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Sample records for added metabolic activation

  1. Somatostatin modulates insulin-degrading-enzyme metabolism: implications for the regulation of microglia activity in AD.

    PubMed

    Tundo, Grazia; Ciaccio, Chiara; Sbardella, Diego; Boraso, Mariaserena; Viviani, Barbara; Coletta, Massimiliano; Marini, Stefano

    2012-01-01

    The deposition of β-amyloid (Aβ) into senile plaques and the impairment of somatostatin-mediated neurotransmission are key pathological events in the onset of Alzheimer's disease (AD). Insulin-degrading-enzyme (IDE) is one of the main extracellular protease targeting Aβ, and thus it represents an interesting pharmacological target for AD therapy. We show that the active form of somatostatin-14 regulates IDE activity by affecting its expression and secretion in microglia cells. A similar effect can also be observed when adding octreotide. Following a previous observation where somatostatin directly interacts with IDE, here we demonstrate that somatostatin regulates Aβ catabolism by modulating IDE proteolytic activity in IDE gene-silencing experiments. As a whole, these data indicate the relevant role played by somatostatin and, potentially, by analogue octreotide, in preventing Aβ accumulation by partially restoring IDE activity.

  2. Fluoride metabolism when added to salt.

    PubMed

    Whitford, Gary M

    2005-01-01

    The purpose of this review is to present the general characteristics of the metabolism of fluoride particularly as it occurs when ingested with fluoridated salt. Following the absorption of salt-borne fluoride from the stomach and intestines, its metabolism is identical to that of water-borne fluoride or other vehicles containing ionized fluoride. Because fluoridated salt is almost always ingested with food, however, absorption from the gastrointestinal tract may be delayed or reduced. Reports dealing with this subject have shown that fluoride absorption is delayed and, therefore, peak plasma concentrations are lower than when fluoride is ingested with water. The amount of ingested fluoride that is finally absorbed, however, is not appreciably affected unless the meal is composed mainly of components with high calcium concentrations. In this case, the extent of absorption can be reduced by as much as 50%. Fluoridated salt is also ingested less frequently than fluoridated water. Data are presented to show that the dose size and frequency of ingestion have only minor effects on fluoride retention in the body and on the concentrations in plasma, bone and enamel. Finally, calculations are presented to show that the risk of acute toxicity from fluoridated salt is virtually non-existent.

  3. Excitation function for deuteron induced nuclear reactions on natural ytterbium for production of high specific activity 177g Lu in no-carrier-added form for metabolic radiotherapy.

    PubMed

    Manenti, Simone; Groppi, Flavia; Gandini, Andrea; Gini, Luigi; Abbas, Kamel; Holzwarth, Uwe; Simonelli, Federica; Bonardi, Mauro

    2011-01-01

    Deuteron-induced nuclear reactions for generation of no-carrier-added Lu radionuclides were investigated using the stacked-foil activation technique on natural Yb targets at energies up to E(d)=18.18 MeV. Excitation functions of the reactions (nat)Yb(d,xn)(169,170,171,172,173,174g,174m,176m,177g)Lu and (nat)Yb(d,pxn)(169,175,177)Yb have been measured, among them three ((169)Lu, (174m)Lu and (176m)Lu) are reported for the first time. The upper limit of the contamination from the long-lived metastable level (177m)Lu was evaluated too. Thick-target yields for all investigated radionuclides are calculated.

  4. Adding biotic complexity alters the metabolic benefits of mutualism.

    PubMed

    Harcombe, William R; Betts, Alex; Shapiro, Jason W; Marx, Christopher J

    2016-08-01

    Mutualism is ubiquitous in nature and plays an integral role in most communities. To predict the eco-evolutionary dynamics of mutualism it is critical to extend classic pair-wise analysis to include additional species. We investigated the effect of adding a third species to a pair-wise mutualism in a spatially structured environment. We tested the hypotheses that selection for costly excretions in a focal population (i) decreases when an exploiter is added (ii) increases when a third mutualist is added relative to the pair-wise scenario. We assayed the selection acting on Salmonella enterica when it exchanges methionine for carbon in an obligate mutualism with an auxotrophic Escherichia coli. A third bacterium, Methylobacterium extorquens, was then added and acted either as an exploiter of the carbon or third obligate mutualist depending on the nitrogen source. In the tripartite mutualism M. extorquens provided nitrogen to the other species. Contrary to our expectations, adding an exploiter increased selection for methionine excretion in S. enterica. Conversely, selection for cooperation was lower in the tripartite mutualism relative to the pair-wise system. Genome-scale metabolic models helped identify the mechanisms underlying these changes in selection. Our results highlight the utility of connecting metabolic mechanisms and eco-evolutionary dynamics. PMID:27272242

  5. POSSIBLE CHROMOSPHERIC ACTIVITY CYCLES IN AD LEO

    SciTech Connect

    Buccino, Andrea P.; Petrucci, Romina; Mauas, Pablo J. D.; Jofré, Emiliano

    2014-01-20

    AD Leo (GJ 388) is an active dM3 flare star that has been extensively observed both in the quiescent and flaring states. Since this active star is near the fully convective boundary, studying its long-term chromospheric activity in detail could be an appreciable contribution to dynamo theory. Here, using the Lomb-Scargle periodogram, we analyze the Ca II K line-core fluxes derived from CASLEO spectra obtained between 2001 and 2013 and the V magnitude from the ASAS database between 2004 and 2010. From both of these totally independent time series, we obtain a possible activity cycle with a period of approximately seven years and a less significant shorter cycle of approximately two years. A tentative interpretation is that a dynamo operating near the surface could be generating the longer cycle, while a second dynamo operating in the deep convection zone could be responsible for the shorter one. Based on the long duration of our observing program at CASLEO and the fact that we observe different spectral features simultaneously, we also analyze the relation between simultaneous measurements of the Na I index (R{sub D}{sup ′}), Hα, and Ca II K fluxes at different activity levels of AD Leo, including flares.

  6. Gender differences of peripheral plasma and liver metabolic profiling in APP/PS1 transgenic AD mice.

    PubMed

    Wu, Junfang; Fu, Bin; Lei, Hehua; Tang, Huiru; Wang, Yulan

    2016-09-22

    Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive impairment. Currently, there is less knowledge of the involvement of the peripheral biofluid/organ in AD, compared with the central nervous system. In addition, with reported high morbidity in women in particular, it has become very important to explore whether gender difference in the peripheral metabolome is associated with AD. Here, we investigated metabolic responses of both plasma and liver tissues using an APP/PS1 double mutant transgenic mouse model with NMR spectroscopy, as well as analysis from serum biochemistry and histological staining. Fatty acid composition from plasma and liver extracts was analyzed using GC-FID/MS. We found clear gender differences in AD transgenic mice when compared with their wild-type counterparts. Female AD mice displayed more intensive responses, which were highlighted by higher levels of lipids, 3-hydroxybutyrate and nucleotide-related metabolites, together with lower levels of glucose. These observations indicate that AD induces oxidative stress and impairs cellular energy metabolism in peripheral organs. Disturbances in AD male mice were milder with depletion of monounsaturated fatty acids. We also observed a higher activity of delta-6-desaturate and suppressed activity of delta-5-desaturate in female mice, whereas inhibited stearoyl-CoA-desaturase in male mice suggested that AD induced by the double mutant genes results in different fatty acids catabolism depending on gender. Our results provide metabolic clues into the peripheral biofluid/organs involved in AD, and we propose that a gender-specific scheme for AD treatment in men and women may be required. PMID:27393253

  7. Variations of 14C around AD 775 and AD 1795 - due to solar activity

    NASA Astrophysics Data System (ADS)

    Neuhäuser, R.; Neuhäuser, D. L.

    2015-12-01

    The motivation for our study is the disputed cause for the strong variation of 14C around AD 775. Our method is to compare the 14C variation around AD 775 with other periods of strong variability. Our results are: (a) We see three periods, where 14C varied over 200 yr in a special way showing a certain pattern of strong secular variation: after a Grand Minimum with strongly increasing 14C, there is a series of strong short-term drop(s), rise(s), and again drop(s) within 60 yr, ending up to 200 yr after the start of the Grand Minimum. These three periods include the strong rises around BC 671, AD 775, and AD 1795. (b) We show with several solar activity proxies (radioisotopes, sunspots, and aurorae) for the AD 770s and 1790s that such intense rapid 14C increases can be explained by strong rapid decreases in solar activity and, hence, wind, so that the decrease in solar modulation potential leads to an increase in radioisotope production. (c) The strong rises around AD 775 and 1795 are due to three effects, (i) very strong activity in the previous cycles (i.e. very low 14C level), (ii) the declining phase of a very strong Schwabe cycle, and (iii) a phase of very weak activity after the strong 14C rise - very short and/or weak cycle(s) like the suddenly starting Dalton minimum. (d) Furthermore, we can show that the strong change at AD 1795 happened after a pair of two packages of four Schwabe cycles with certain hemispheric leadership (each package consists of two Gnevyshev-Ohl pairs, respectively two Hale-Babcock pairs). We show with several additional arguments that the rise around AD 775 was not that special. We conclude that such large, short-term rises in 14C (around BC 671, AD 775, and 1795) do not need to be explained by highly unlikely solar super-flares nor other rare events, but by extra-solar cosmic rays modulated due to solar activity variations.

  8. Characterization of the Gene Cluster Involved in Isoprene Metabolism in Rhodococcus sp. Strain AD45

    PubMed Central

    van Hylckama Vlieg, Johan E. T.; Leemhuis, Hans; Spelberg, Jeffrey H. Lutje; Janssen, Dick B.

    2000-01-01

    The genes involved in isoprene (2-methyl-1,3-butadiene) utilization in Rhodococcus sp. strain AD45 were cloned and characterized. Sequence analysis of an 8.5-kb DNA fragment showed the presence of 10 genes of which 2 encoded enzymes which were previously found to be involved in isoprene degradation: a glutathione S-transferase with activity towards 1,2-epoxy-2-methyl-3-butene (isoI) and a 1-hydroxy-2-glutathionyl-2-methyl-3-butene dehydrogenase (isoH). Furthermore, a gene encoding a second glutathione S-transferase was identified (isoJ). The isoJ gene was overexpressed in Escherichia coli and was found to have activity with 1-chloro-2,4-dinitrobenzene and 3,4-dichloro-1-nitrobenzene but not with 1,2-epoxy-2-methyl-3-butene. Downstream of isoJ, six genes (isoABCDEF) were found; these genes encoded a putative alkene monooxygenase that showed high similarity to components of the alkene monooxygenase from Xanthobacter sp. strain Py2 and other multicomponent monooxygenases. The deduced amino acid sequence encoded by an additional gene (isoG) showed significant similarity with that of α-methylacyl-coenzyme A racemase. The results are in agreement with a catabolic route for isoprene involving epoxidation by a monooxygenase, conjugation to glutathione, and oxidation of the hydroxyl group to a carboxylate. Metabolism may proceed by fatty acid oxidation after removal of glutathione by a still-unknown mechanism. PMID:10715003

  9. Improved vitamin B12 fermentation process by adding rotenone to regulate the metabolism of Pseudomonas denitrificans.

    PubMed

    Cheng, Xin; Chen, Wei; Peng, Wei-Fu; Li, Kun-Tai

    2014-06-01

    Our previous research had revealed that the dissolved oxygen limitation was more favorable for vitamin B12 fermentation, due to its inducement to the increased glycolytic flux in Pseudomonas denitrificans. In this paper, a novel strategy was implemented to further investigate the metabolic characteristics of P. denitrificans under different oxygen supply levels, by exogenously adding rotenone (a respiratory chain inhibitor interfering with the oxygen consumption) to the fermentation broths. Compared to the fermentation process without rotenone treatment, it was observed that 5 mg/L rotenone treatment could significantly strengthen the glycolytic flux of P. denitrificans via activating the key glycolytic enzymes (phosphofructokinase and pyruvate kinase), resulting in the accelerated generations of anterior precursors (glutamate and 5-aminolevulinic acid) for vitamin B12 biosynthesis. Although 5 mg/L rotenone treatment had a negative effect on cell growth of P. denitrificans, the vitamin B12 yield was increased from 48.28 ± 0.62 mg/L to 54.70 ± 0.45 mg/L, which further proved that an increased glycolytic flux in P. denitrificans was a consequence of higher vitamin B12 production. PMID:24687557

  10. Viscosity dictates metabolic activity of Vibrio ruber

    PubMed Central

    Borić, Maja; Danevčič, Tjaša; Stopar, David

    2012-01-01

    Little is known about metabolic activity of bacteria, when viscosity of their environment changes. In this work, bacterial metabolic activity in media with viscosity ranging from 0.8 to 29.4 mPas was studied. Viscosities up to 2.4 mPas did not affect metabolic activity of Vibrio ruber. On the other hand, at 29.4 mPas respiration rate and total dehydrogenase activity increased 8 and 4-fold, respectively. The activity of glucose-6-phosphate dehydrogenase (GPD) increased up to 13-fold at higher viscosities. However, intensified metabolic activity did not result in faster growth rate. Increased viscosity delayed the onset as well as the duration of biosynthesis of prodigiosin. As an adaptation to viscous environment V. ruber increased metabolic flux through the pentose phosphate pathway and reduced synthesis of a secondary metabolite. In addition, V. ruber was able to modify the viscosity of its environment. PMID:22826705

  11. Metabolic rate of carrying added mass: a function of walking speed, carried mass and mass location.

    PubMed

    Schertzer, Eliran; Riemer, Raziel

    2014-11-01

    The effort of carrying additional mass at different body locations is important in ergonomics and in designing wearable robotics. We investigate the metabolic rate of carrying a load as a function of its mass, its location on the body and the subject's walking speed. Novel metabolic rate prediction equations for walking while carrying loads at the ankle, knees and back were developed based on experiments where subjects walked on a treadmill at 4, 5 or 6km/h bearing different amounts of added mass (up to 2kg per leg and 22kg for back). Compared to previously reported equations, ours are 7-69% more accurate. Results also show that relative cost for carrying a mass at a distal versus a proximal location changes with speed and mass. Contrary to mass carried on the back, mass attached to the leg cannot be modeled as an increase in body mass. PMID:24793822

  12. Solar activity around AD 775 from aurorae and radiocarbon

    NASA Astrophysics Data System (ADS)

    Neuhäuser, R.; Neuhäuser, D. L.

    2015-04-01

    A large variation in 14C around AD 775 has been considered to be caused by one or more solar super-flares within one year. We critically review all known aurora reports from Europe as well as the Near, Middle, and Far East from AD 731 to 825 and find 39 likely true aurorae plus four more potential aurorae and 24 other reports about halos, meteors, thunderstorms etc., which were previously misinterpreted as aurorae or misdated; we assign probabilities for all events according to five aurora criteria. We find very likely true aurorae in AD 743, 745, 762, 765, 772, 773, 793, 796, 807, and 817. There were two aurorae in the early 770s observed near Amida (now Diyarbak\\i r in Turkey near the Turkish-Syrian border), which were not only red, but also green-yellow - being at a relatively low geomagnetic latitude, they indicate a relatively strong solar storm. However, it cannot be argued that those aurorae (geomagnetic latitude 43 to 50°, considering five different reconstructions of the geomagnetic pole) could be connected to one or more solar super-flares causing the 14C increase around AD 775: There are several reports about low- to mid-latitude aurorae at 32 to 44° geomagnetic latitude in China and Iraq; some of them were likely observed (quasi-)simultaneously in two of three areas (Europe, Byzantium/Arabia, East Asia), one lasted several nights, and some indicate a particularly strong geomagnetic storm (red colour and dynamics), namely in AD 745, 762, 793, 807, and 817 - always without 14C peaks. We use 39 likely true aurorae as well as historic reports about sunspots together with the radiocarbon content from tree rings to reconstruct the solar activity: From AD {˜ 733} to {˜ 823}, we see at least nine Schwabe cycles; instead of one of those cycles, there could be two short, weak cycles - reflecting the rapid increase to a high 14C level since AD 775, which lies at the end of a strong cycle. In order to show the end of the dearth of naked-eye sunspots, we

  13. A Guide to Microsoft Active Directory (AD) Design

    SciTech Connect

    Dias, J

    2002-04-29

    The goal of this paper is to facilitate the design process for those DOE sites that are currently engaged in designing their Active Directory (AD) network. It is a roadmap to enable analysis of the complicated design tradeoffs associated with Active Directory Design. By providing discussion of Active Directory design elements which are permanent and costly to change once deployed, the hope is to minimize the risks of sponsoring failed designs, or joining existing infrastructures not suitable to programmatic needs. Specifically, most Active Directory structures will fall under one of three common designs: Single Domain, Single Forest with Multiple Domains, or Multiple Forests. Each has benefits and concerns, depending on programmatic and organizational structures. The comparison of these three approaches will facilitate almost any Active Directory design effort. Finally, this paper describes some best practices to consider when designing Active Directory based on three years of research and experience.

  14. Industry as a metabolic activity.

    PubMed

    Smart, B

    1992-02-01

    The concept of "industrial economic metabolism" can provide a bridge to better understanding between environmentalists and industry. In nature each individual or species reacts to natural stimuli, competing with others for resources, extending its domain until it loses comparative advantage and comes to equilibrium with an adjacent competitor. Those species that succeed over time flourish; those that do not, diminish or disappear. Nature's rule book has no moral or ethical ingredient beyond self-interest. Corporate metabolisms are remarkably similar to those of nature. They too react to stimuli, collect and use resources, and grow or perish based on how effectively they compete. Corporate management recognizes and responds naturally and efficiently to cost and price signals. Through them it selects resources and converts them into useful products. The efficiency with which this is done is measured by profit, the lifeblood of the corporation and its means of growth. Profit thus provides a discipline on corporate behavior, encouraging efficient performers, and, by its absence, weeding out others. Unfettered by influences other than economics, the path to corporate success is unlikely to be a compassionate one. The dilemma of the manager is that to do what is socially "right" often conflicts with what must be done to survive and prosper. Fortunately, corporations' behavior can be altered by society when their purely economic role comes into conflict with other human values. The environment and the economy are not separate systems but intertwined to form a complex natural and social setting. The human-designed economic system depends on natural resource inputs, and in turn its metabolic wastes can overload the ecological system, threatening the long-term survivability of both. Increasing concern for the environment now gives the farsighted manager new latitude. There are competitive benefits in some pollution prevention. But there are not sufficiently strong forces to

  15. Microbial metabolic activity in soil as measured by dehydrogenase determinations

    NASA Technical Reports Server (NTRS)

    Casida, L. E., Jr.

    1977-01-01

    The dehydrogenase technique for measuring the metabolic activity of microorganisms in soil was modified to use a 6-h, 37 C incubation with either glucose or yeast extract as the electron-donating substrate. The rate of formazan production remained constant during this time interval, and cellular multiplication apparently did not occur. The technique was used to follow changes in the overall metabolic activities of microorganisms in soil undergoing incubation with a limiting concentration of added nutrient. The sequence of events was similar to that obtained by using the Warburg respirometer to measure O2 consumption. However, the major peaks of activity occurred earlier with the respirometer. This possibly is due to the lack of atmospheric CO2 during the O2 consumption measurements.

  16. Effects of long-term treatment with pioglitazone on cognition and glucose metabolism of PS1-KI, 3xTg-AD, and wild-type mice.

    PubMed

    Masciopinto, F; Di Pietro, N; Corona, C; Bomba, M; Pipino, C; Curcio, M; Di Castelnuovo, A; Ciavardelli, D; Silvestri, E; Canzoniero, L M T; Sekler, I; Pandolfi, A; Sensi, S L

    2012-12-20

    In this study, we investigated the effects of long-term (9-month) treatment with pioglitazone (PIO; 20 mg/kg/d) in two animal models of Alzheimer's disease (AD)-related neural dysfunction and pathology: the PS1-KI(M146V) (human presenilin-1 (M146V) knock-in mouse) and 3xTg-AD (triple transgenic mouse carrying AD-linked mutations) mice. We also investigated the effects on wild-type (WT) mice. Mice were monitored for body mass changes, fasting glycemia, glucose tolerance, and studied for changes in brain mitochondrial enzyme activity (complexes I and IV) as well as energy metabolism (lactate dehydrogenase (LDH)). Cognitive effects were investigated with the Morris water maze (MWM) test and the object recognition task (ORT). Behavioral analysis revealed that PIO treatment promoted positive cognitive effects in PS1-KI female mice. These effects were associated with normalization of peripheral gluco-regulatory abnormalities that were found in untreated PS1-KI females. PIO-treated PS1-KI females also showed no statistically significant alterations in brain mitochondrial enzyme activity but significantly increased reverse LDH activity.PIO treatment produced no effects on cognition, glucose metabolism, or mitochondrial functioning in 3xTg-AD mice. Finally, PIO treatment promoted enhanced short-term memory performance in WT male mice, a group that did not show deregulation of glucose metabolism but that showed decreased activity of complex I in hippocampal and cortical mitochondria. Overall, these results indicate metabolically driven cognitive-enhancing effects of PIO that are differentially gender-related among specific genotypes.

  17. Quiescent Fibroblasts Exhibit High Metabolic Activity

    PubMed Central

    Lemons, Johanna M. S.; Feng, Xiao-Jiang; Bennett, Bryson D.; Legesse-Miller, Aster; Johnson, Elizabeth L.; Raitman, Irene; Pollina, Elizabeth A.; Rabitz, Herschel A.; Rabinowitz, Joshua D.; Coller, Hilary A.

    2010-01-01

    Many cells in mammals exist in the state of quiescence, which is characterized by reversible exit from the cell cycle. Quiescent cells are widely reported to exhibit reduced size, nucleotide synthesis, and metabolic activity. Much lower glycolytic rates have been reported in quiescent compared with proliferating lymphocytes. In contrast, we show here that primary human fibroblasts continue to exhibit high metabolic rates when induced into quiescence via contact inhibition. By monitoring isotope labeling through metabolic pathways and quantitatively identifying fluxes from the data, we show that contact-inhibited fibroblasts utilize glucose in all branches of central carbon metabolism at rates similar to those of proliferating cells, with greater overflow flux from the pentose phosphate pathway back to glycolysis. Inhibition of the pentose phosphate pathway resulted in apoptosis preferentially in quiescent fibroblasts. By feeding the cells labeled glutamine, we also detected a “backwards” flux in the tricarboxylic acid cycle from α-ketoglutarate to citrate that was enhanced in contact-inhibited fibroblasts; this flux likely contributes to shuttling of NADPH from the mitochondrion to cytosol for redox defense or fatty acid synthesis. The high metabolic activity of the fibroblasts was directed in part toward breakdown and resynthesis of protein and lipid, and in part toward excretion of extracellular matrix proteins. Thus, reduced metabolic activity is not a hallmark of the quiescent state. Quiescent fibroblasts, relieved of the biosynthetic requirements associated with generating progeny, direct their metabolic activity to preservation of self integrity and alternative functions beneficial to the organism as a whole. PMID:21049082

  18. Metabolic Activity - Skylab Experiment M171

    NASA Technical Reports Server (NTRS)

    1972-01-01

    This chart details Skylab's Metabolic Activity experiment (M171), a medical evaluation facility designed to measure astronauts' metabolic changes while on long-term space missions. The experiment obtained information on astronauts' physiological capabilities and limitations and provided data useful in the design of future spacecraft and work programs. Physiological responses to physical activity was deduced by analyzing inhaled and exhaled air, pulse rate, blood pressure, and other selected variables of the crew while they performed controlled amounts of physical work with a bicycle ergometer. The Marshall Space Flight Center had program responsibility for the development of Skylab hardware and experiments.

  19. Physical activity attenuates age-related biomarker alterations in preclinical AD

    PubMed Central

    Schultz, Stephanie A.; Oh, Jennifer M.; Larson, Jordan; Edwards, Dorothy; Cook, Dane; Koscik, Rebecca; Gallagher, Catherine L.; Dowling, N.M.; Carlsson, Cynthia M.; Bendlin, Barbara B.; LaRue, Asenath; Rowley, Howard A.; Christian, Brad T.; Asthana, Sanjay; Hermann, Bruce P.; Johnson, Sterling C.; Sager, Mark A.

    2014-01-01

    Objective: To examine whether engagement in physical activity might favorably alter the age-dependent evolution of Alzheimer disease (AD)-related brain and cognitive changes in a cohort of at-risk, late-middle-aged adults. Methods: Three hundred seventeen enrollees in the Wisconsin Registry for Alzheimer's Prevention underwent T1 MRI; a subset also underwent 11C-Pittsburgh compound B–PET (n = 186) and 18F-fluorodeoxyglucose–PET (n = 152) imaging. Participants' responses on a self-report measure of current physical activity were used to classify them as either physically active or physically inactive based on American Heart Association guidelines. They also completed a comprehensive neuropsychological battery. Covariate-adjusted regression analyses were used to test whether the adverse effect of age on imaging and cognitive biomarkers was modified by physical activity. Results: There were significant age × physical activity interactions for β-amyloid burden (p = 0.014), glucose metabolism (p = 0.015), and hippocampal volume (p = 0.025) such that, with advancing age, physically active individuals exhibited a lesser degree of biomarker alterations compared with the physically inactive. Similar age × physical activity interactions were also observed on cognitive domains of Immediate Memory (p = 0.042) and Visuospatial Ability (p = 0.016). In addition, the physically active group had higher scores on Speed and Flexibility (p = 0.002) compared with the inactive group. Conclusions: In a middle-aged, at-risk cohort, a physically active lifestyle is associated with an attenuation of the deleterious influence of age on key biomarkers of AD pathophysiology. However, because our observational, cross-sectional design cannot establish causality, randomized controlled trials/longitudinal studies will be necessary for determining whether midlife participation in structured physical exercise forestalls the development of AD and related disorders in later life. PMID:25298312

  20. METABOLISM AND METABOLIC ACTIVATION OF CHEMICALS: IN-SILICO SIMULATION

    EPA Science Inventory

    The role of metabolism in prioritizing chemicals according to their potential adverse health effects is extremely important because innocuous parents can be transformed into toxic metabolites. This work presents the TIssue MEtabolism Simulator (TIMES) platform for simulating met...

  1. Metabolic activity of microorganisms in evaporites

    NASA Technical Reports Server (NTRS)

    Rothschild, L. J.; Giver, L. J.; White, M. R.; Mancinelli, R. L.

    1994-01-01

    Crystalline salt is generally considered so hostile to most forms of life that it has been used for centuries as a preservative. Here, we present evidence that prokaryotes inhabiting a natural evaporite crust of halite and gypsum are metabolically active while inside the evaporite for at least 10 months. In situ measurements demonstrated that some of these "endoevaporitic" microorganisms (probably the cyanobacterium Synechococcus Nageli) fixed carbon and nitrogen. Denitrification was not observed. Our results quantified the slow microbial activity that can occur in salt crystals. Implications of this study include the possibility that microorganisms found in ancient evaporite deposits may have been part of an evaporite community.

  2. Metabolic activity of microorganisms in evaporites.

    PubMed

    Rothschild, L J; Giver, L J; White, M R; Mancinelli, R L

    1994-06-01

    Crystalline salt is generally considered so hostile to most forms of life that it has been used for centuries as a preservative. Here, we present evidence that prokaryotes inhabiting a natural evaporite crust of halite and gypsum are metabolically active while inside the evaporite for at least 10 months. In situ measurements demonstrated that some of these "endoevaporitic" microorganisms (probably the cyanobacterium Synechococcus Nageli) fixed carbon and nitrogen. Denitrification was not observed. Our results quantified the slow microbial activity that can occur in salt crystals. Implications of this study include the possibility that microorganisms found in ancient evaporite deposits may have been part of an evaporite community. PMID:11539827

  3. Metabolic activity of microorganisms in evaporites.

    PubMed

    Rothschild, L J; Giver, L J; White, M R; Mancinelli, R L

    1994-06-01

    Crystalline salt is generally considered so hostile to most forms of life that it has been used for centuries as a preservative. Here, we present evidence that prokaryotes inhabiting a natural evaporite crust of halite and gypsum are metabolically active while inside the evaporite for at least 10 months. In situ measurements demonstrated that some of these "endoevaporitic" microorganisms (probably the cyanobacterium Synechococcus Nageli) fixed carbon and nitrogen. Denitrification was not observed. Our results quantified the slow microbial activity that can occur in salt crystals. Implications of this study include the possibility that microorganisms found in ancient evaporite deposits may have been part of an evaporite community.

  4. Ideal free distribution of metabolic activity: Implications of seasonal metabolic-activity patterns on competitive coexistence.

    PubMed

    Szabó, Péter

    2016-10-01

    The seasonal distribution of metabolic activity determines how much individuals experience different aspects of a periodically changing environment. Seasonal metabolic-activity patterns of coexisting species may differ significantly despite their shared environmental conditions, suggesting that interspecific diversification of this trait has a major role in the coexistence of competing species. In the present study the effect of the seasonal distribution of metabolic activity on intra- and interspecific competition is investigated in a consumer-resource model. It is shown that, in a periodically changing environment, for each environmental preference pattern there is an ideal seasonal distribution of metabolic activity, which results in maximum resource utilisation efficiency and competitive superiority. Contrary to the common interpretation of temporal niche segregation, opposing species-specific seasonal preferences are not a sufficient condition for the coexistence of two species on a population dynamical time scale. A necessary and sufficient condition for coexistence is the temporal segregation of the species via different seasonal activity distributions. However, coexistence is evolutionarily stable only if seasonal metabolic activities and preferences are positively correlated. PMID:27189108

  5. Gastrocnemius and soleus are selectively activated when adding knee extensor activity to plantar flexion.

    PubMed

    Suzuki, Takahito; Chino, Kentaro; Fukashiro, Senshi

    2014-08-01

    The gastrocnemius is a biarticular muscle that acts not only as a plantar flexor, but also as a knee flexor, meaning that it is an antagonist during knee extension. In contrast, the soleus is a monoarticular plantar flexor. Based on this anatomical difference, these muscles' activities should be selectively activated during simultaneous plantar flexion and knee extension, which occur during many activities of daily living. This study examined the selective activation of gastrocnemius and soleus activities when voluntary isometric activation of knee extensors was added to voluntary isometric plantar flexion. Ten male volunteers performed isometric plantar flexion at 10%, 20%, and 30% of maximum effort. During each plantar flexion task, isometric knee extension was added at 0%, 50%, and 100% of maximum effort. When knee extension was added, the average rectified value of the electromyographic activity of the medial gastrocnemius was significantly depressed (P=.002), whereas that of the soleus was significantly increased (P<.001) regardless of the plantar flexion level. These results suggest that plantar flexion with concurrent knee extensor activity leads to selective activation of the soleus and depression of the synergistic activity of the gastrocnemius.

  6. Metabolic assessments during extra-vehicular activity

    NASA Astrophysics Data System (ADS)

    Osipov, Yu. Yu.; Spichkov, A. N.; Filipenkov, S. N.

    Extra-vehicular activity (EVA) has a significant role during extended space flights. It demonstrates that humans can survive and perform useful work outside the Orbital Space Stations (OSS) while wearing protective space suits (SS). When the International Space Station 'Alpha'(ISSA) is fully operational, EVA assembly, installation, maintenance and repair operations will become an everyday repetitive work activity in space. It needs new ergonomic evaluation of the work/rest schedule for an increasing of the labor amount per EVA hour. The metabolism assessment is a helpful method to control the productivity of the EVA astronaut and to optimize the work/rest regime. Three following methods were used in Russia to estimate real-time metabolic rates during EVA: 1. Oxygen consumption, computed from the pressure drop in a high pressure bottle per unit time (with actual thermodynamic oxygen properties under high pressure and oxygen leakage taken into account). 2. Carbon dioxide production, computed from CO 2 concentration at the contaminant control cartridge and gas flow rate in the life support subsystem closed loop (nominal mode) or gas leakage in the SS open loop (emergency mode). 3. Heat removal, computed from the difference between the temperatures of coolant water or gas and its flow rate in a unit of time (with assumed humidity and wet oxygen state taken into account). Comparison of heat removal values with metabolic rates enables us to determine the thermal balance during an operative medical control of EVA at "Salyut-6", "Salyut-7" and "Mir" OSS. Complex analysis of metabolism, body temperature and heat rate supports a differential diagnosis between emotional and thermal components of stress during EVA. It gives a prognosis of human homeostasis during EVA. Available information has been acquired into an EVA data base which is an effective tool for ergonomical optimization.

  7. Metabolic effects of adding sucrose and aspartame to the diet of subjects with noninsulin-dependent diabetes mellitus.

    PubMed

    Colagiuri, S; Miller, J J; Edwards, R A

    1989-09-01

    This study compared the effects of adding sucrose and aspartame to the usual diet of individuals with well-controlled noninsulin-dependent diabetes mellitus (NIDDM). A double-blind, cross-over design was used with each 6-wk study period. During the sucrose period, 45 g sucrose (9% of total daily energy) was added, 10 g with each main meal and 5 g with each between-meal beverage. An equivalent sweetening quantity of aspartame (162 mg) was ingested during the aspartame period. The addition of sucrose did not have a deleterious effect on glycemic control, lipids, glucose tolerance, or insulin action. No differences were observed between sucrose and aspartame. Sucrose added as an integral part of the diabetic diet does not adversely affect metabolic control in well-controlled NIDDM subjects. Aspartame is an acceptable sugar substitute for diabetic individuals but no specific advantage over sucrose was demonstrated.

  8. Physical activity as a metabolic stressor.

    PubMed

    Coyle, E F

    2000-08-01

    Both physical activity and diet stimulate processes that, over time, alter the morphologic composition and biochemical function of the body. Physical activity provides stimuli that promote very specific and varied adaptations according to the type, intensity, and duration of exercise performed. There is further interest in the extent to which diet or supplementation can enhance the positive stimuli. Prolonged walking at low intensity presents little metabolic, hormonal, or cardiovascular stress, and the greatest perturbation from rest appears to be from increased fat oxidation and plasma free fatty acid mobilization resulting from a combination of increased lipolysis and decreased reesterification. More intense jogging or running largely stimulates increased oxidation of glycogen and triacylglycerol, both of which are stored directly within the muscle fibers. Furthermore, these intramuscular stores of carbohydrate and fat appear to be the primary substrates for the enhanced oxidative and performance ability derived from endurance training-induced increases in muscle mitochondrial density. Weightlifting that produces fatigue in brief periods (ie, in 15-90 s and after 15 repetitive contractions) elicits a high degree of motor unit recruitment and muscle fiber stimulation. This is a remarkably potent stimulus for altering protein synthesis in muscle and increasing neuromuscular function. The metabolic stress of physical activity can be measured by substrate turnover and depletion, cardiovascular response, hormonal perturbation, accumulation of metabolites, or even the extent to which the synthesis and degradation of specific proteins are altered, either acutely or by chronic exercise training. PMID:10919953

  9. Metabolically active functional food ingredients for weight control.

    PubMed

    Kovacs, E M R; Mela, D J

    2006-02-01

    The scale of the obesity epidemic creates a pressing consumer need as well as an enormous business opportunity for successful development and marketing of food products with added benefits for weight control. A number of proposed functional food ingredients have been shown to act post-absorptively to influence substrate utilization or thermogenesis. Characteristics and supporting data on conjugated linoleic acid, diglycerides, medium-chain triglycerides, green tea, ephedrine, caffeine, capsaicin and calcium, are reviewed here, giving examples of how these could act to alter energy expenditure or appetite control. Consideration is also given to other factors, in addition to efficacy, which must be satisfied to get such ingredients into foods. We conclude that, for each of the safe, putatively metabolically active agents, there remain gaps in clinical evidence or knowledge of mechanisms, which need to be addressed in order to specify the dietary conditions and food product compositions where these ingredients could be of most benefit for weight control. PMID:16436103

  10. Metabolic Activity of Bacteria at High Pressure

    NASA Astrophysics Data System (ADS)

    Picard, A.; Daniel, I.; Oger, P.

    2008-12-01

    a depth of marine sediment of 500 m, or even beneath a water column of 6 km in surface sediments. This suggests that the metabolic activity of surface microorganisms that receive nutrients through sea water percolation into the deeper parts of the sediment, or that sink with the sediment, may represent a significant fraction of the total activity observed in subsurface environments. The present results indicate also that cells in stationary phase at HHP, which preclude growth, can still have a short-term metabolic activity independent of the growth-related activity. Consequently, surface microorganisms have the ability to impact significantly and rapidly on biogeochemical cycles in deep environments.

  11. Survival of added bacterial species and metabolism of toxic compounds in natural environments

    SciTech Connect

    King, V.M.

    1987-01-01

    Bacteria able to degrade either 2,4-dichlorophenol (DCP) or phenanthrene (PHEN) were isolated from polluted freshwater environments. Two isolates able to degrade each compound were tested for mineralization with a sensitive /sup 14/C assay and for survival in lake water and sewage using a selective medium. One DCP isolate was identified as Alcaligenes paradoxus and the other as Alcaligenes sp. One PHEN isolate was identified as Pseudomonas fluorescens and the other as Pseudomonas sp. All four isolates survived and grew in sterile environments which indicated that starvation would not be a factor in survival of these strains. The number of organisms declined immediately in number in nonsterile lake water. However, they did survive or even grow in nonsterile sewage for a short period before declining in number. Biotic factors appeared to be influential for survival and mineralization of target compounds in many environments. The removal of protozoa, which prey on bacteria, improved survival of the added cells, but had no influence on the mineralization of 10 ..mu..g DCP/L. In comparison, degradation of 10 and 25 mg DCP/L stopped after a few days. Yeast nitrogen base appeared to overcome the lack of nutrient regeneration, a function attributed to protozoa. The additional nutrients increased toxicant mineralization, especially when seeded with appropriate species. Thus, protozoa may limit growth of added cells but appear to be needed for mineralization of higher concentrations of DCP.

  12. Adding two active silver atoms on Au₂₅ nanoparticle.

    PubMed

    Yao, Chuanhao; Chen, Jishi; Li, Man-Bo; Liu, Liren; Yang, Jinlong; Wu, Zhikun

    2015-02-11

    Alloy nanoparticles with atomic monodispersity is of importance for some fundamental research (e.g., the investigation of active sites). However, the controlled preparation of alloy nanoparticles with atomic monodispersity has long been a major challenge. Herein, for the first time a unique method, antigalvanic reduction (AGR), is introduced to synthesize atomically monodisperse Au25Ag2(SC2H4Ph)18 in high yield (89%) within 2 min. Interestingly, the two silver atoms in Au25Ag2(SC2H4Ph)18 do not replace the gold atoms in the precursor particle Au25(SC2H4Ph)18 but collocate on Au25, which was supported by experimental and calculated results. Also, the two silver atoms are active to play roles in stabilizing the alloy nanoparticle, triggering the nanoparticle fluorescence and catalyzing the hydrolysis of 1,3-diphenylprop-2-ynyl acetate. PMID:25580617

  13. Diverse Activities of Histone Acylations Connect Metabolism to Chromatin Function.

    PubMed

    Dutta, Arnob; Abmayr, Susan M; Workman, Jerry L

    2016-08-18

    Modifications of histones play important roles in balancing transcriptional output. The discovery of acyl marks, besides histone acetylation, has added to the functional diversity of histone modifications. Since all modifications use metabolic intermediates as substrates for chromatin-modifying enzymes, the prevalent landscape of histone modifications in any cell type is a snapshot of its metabolic status. Here, we review some of the current findings of how differential use of histone acylations regulates gene expression as response to metabolic changes and differentiation programs. PMID:27540855

  14. Exenatide promotes cognitive enhancement and positive brain metabolic changes in PS1-KI mice but has no effects in 3xTg-AD animals.

    PubMed

    Bomba, M; Ciavardelli, D; Silvestri, E; Canzoniero, L M T; Lattanzio, R; Chiappini, P; Piantelli, M; Di Ilio, C; Consoli, A; Sensi, S L

    2013-05-02

    Recent studies have shown that type 2 diabetes mellitus (T2DM) is a risk factor for cognitive dysfunction or dementia. Insulin resistance is often associated with T2DM and can induce defective insulin signaling in the central nervous system as well as increase the risk of cognitive impairment in the elderly. Glucagone like peptide-1 (GLP-1) is an incretin hormone and, like GLP-1 analogs, stimulates insulin secretion and has been employed in the treatment of T2DM. GLP-1 and GLP-1 analogs also enhance synaptic plasticity and counteract cognitive deficits in mouse models of neuronal dysfunction and/or degeneration. In this study, we investigated the potential neuroprotective effects of long-term treatment with exenatide, a GLP-1 analog, in two animal models of neuronal dysfunction: the PS1-KI and 3xTg-AD mice. We found that exenatide promoted beneficial effects on short- and long-term memory performances in PS1-KI but not in 3xTg-AD animals. In PS1-KI mice, the drug increased brain lactate dehydrogenase activity leading to a net increase in lactate levels, while no effects were observed on mitochondrial respiration. On the contrary, exenatide had no effects on brain metabolism of 3xTg-AD mice. In summary, our data indicate that exenatide improves cognition in PS1-KI mice, an effect likely driven by increasing the brain anaerobic glycolysis rate.

  15. Exenatide promotes cognitive enhancement and positive brain metabolic changes in PS1-KI mice but has no effects in 3xTg-AD animals

    PubMed Central

    Bomba, M; Ciavardelli, D; Silvestri, E; Canzoniero, L MT; Lattanzio, R; Chiappini, P; Piantelli, M; Di Ilio, C; Consoli, A; Sensi, S L

    2013-01-01

    Recent studies have shown that type 2 diabetes mellitus (T2DM) is a risk factor for cognitive dysfunction or dementia. Insulin resistance is often associated with T2DM and can induce defective insulin signaling in the central nervous system as well as increase the risk of cognitive impairment in the elderly. Glucagone like peptide-1 (GLP-1) is an incretin hormone and, like GLP-1 analogs, stimulates insulin secretion and has been employed in the treatment of T2DM. GLP-1 and GLP-1 analogs also enhance synaptic plasticity and counteract cognitive deficits in mouse models of neuronal dysfunction and/or degeneration. In this study, we investigated the potential neuroprotective effects of long-term treatment with exenatide, a GLP-1 analog, in two animal models of neuronal dysfunction: the PS1-KI and 3xTg-AD mice. We found that exenatide promoted beneficial effects on short- and long-term memory performances in PS1-KI but not in 3xTg-AD animals. In PS1-KI mice, the drug increased brain lactate dehydrogenase activity leading to a net increase in lactate levels, while no effects were observed on mitochondrial respiration. On the contrary, exenatide had no effects on brain metabolism of 3xTg-AD mice. In summary, our data indicate that exenatide improves cognition in PS1-KI mice, an effect likely driven by increasing the brain anaerobic glycolysis rate. PMID:23640454

  16. Correlations of regional postmortem enzyme activities with premortem local glucose metabolic rates in Alzheimer's disease.

    PubMed

    McGeer, E G; McGeer, P L; Harrop, R; Akiyama, H; Kamo, H

    1990-12-01

    Correlations were sought between local cerebral metabolic rates (LCMRs) for glucose in various regions of the cortex, determined in premortem PET scans, with the regional activities of choline acetyltransferase (ChAT), acetylcholinesterase (AChE), beta-glucuronidase (Gluc, a probable index of reactive gliosis), and phosphate-activated glutaminase (PAG, a possible indice of the large pyramidal neurons) measured on postmortem tissue. Significant negative correlations between LCMRs and Gluc activities were found in 6 PET-scanned cases of Alzheimer disease (AD), and positive correlations of LCMRs with PAG were found in 5. By contrast, a positive correlation with ChAT and AChE was found in only 1. The results are consistent with the metabolic deficits in AD being primarily a reflection of local neuronal loss and gliosis. Similar data on two cases of Huntington's disease showed no significant correlations, while 1 patient with Parkinson dementia showed a significant (negative) correlation only with Gluc.

  17. Evidence for metabolic activity of airborne bacteria

    NASA Technical Reports Server (NTRS)

    Chatigny, M. A.; Wolochow, H.

    1974-01-01

    Aerosols of the bacterium Serratia marcescens, and of uniformly labeled C-14 glucose were produced simultaneously and mixed in tubing leading to an aerosol chamber. During a subsequent period of about 5 hrs, carbon dioxide was produced metabolically within the chamber, and labeled material incorporated within the suspended particles first increased then decreased. This constitutes the first direct evidence of microbial metabolism of bacteria suspended in the air.

  18. Mediators of sympathetic activation in metabolic syndrome obesity.

    PubMed

    Straznicky, Nora E; Eikelis, Nina; Lambert, Elisabeth A; Esler, Murray D

    2008-12-01

    The metabolic syndrome represents a major public health burden because of its high prevalence in the general population and its association with cardiovascular disease and type 2 diabetes. Accumulated evidence based on biochemical, neurophysiologic, and indirect measurements of autonomic activity indicate that visceral obesity and the metabolic syndrome are associated with enhanced sympathetic neural drive and vagal impairment. The mechanisms linking metabolic syndrome with sympathetic activation are complex and not completely understood, and cause-effect relationships need further clarification from prospective trials. Components of the metabolic syndrome that may directly or indirectly enhance sympathetic drive include hyperinsulinemia, leptin, nonesterified fatty acids, proinflammatory cytokines, angiotensinogen, baroreflex impairment, and obstructive sleep apnea. beta-Adrenoceptor polymorphisms have also been associated with adrenoceptor desensitization, increased adiposity, insulin resistance, and enhanced sympathetic activity. Because chronic sympathetic activation contributes to hypertension and its target-organ damage, sympathoinhibition remains an important goal in the therapeutic management of the metabolic syndrome.

  19. Microstructural and phase evolution in metakaolin geopolymers with different activators and added aluminosilicate fillers

    NASA Astrophysics Data System (ADS)

    Sarkar, Madhuchhanda; Dana, Kausik; Das, Sukhen

    2015-10-01

    This work aims to investigate the microstructural and phase evolution of alkali activated metakaolin products with different activators and added aluminosilicate filler phases. The added filler phases have different reactivity to the alkali activated metakaolin system. Microstructural evolution in the alkali activated products has been investigated by X-ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR) and Field Emission Scanning Electron Microscope (FESEM). Variation in strength development in alkali activated metakaolin products was followed by compressive strength measurement test. Microstructural study shows that in case of metakaolin with NaOH activator crystalline sodalite formed in all the product samples irrespective of the added filler phases. The microstructure of these NaOH activated products investigated by FESEM showed crystalline and inhomogeneous morphology. Mixed activator containing both NaOH and sodium silicate in a fixed mass ratio formed predominantly amorphous phase. Microstructure of these samples showed more homogeneity than that of NaOH activated metakaolin products. The study further shows that addition of α-Al2O3 powder, non reactive phase to the alkali activated metakaolin system when used in larger amount increased crystalline phase in the matrix. α-Al2O3 powder addition increased the compressive strength of the product samples for both the activator compositions. Added phase of colloidal silica, reactive to the alkali activated metakaolin system when used in larger amount was found to increase amorphous nature of the matrix. Addition of colloidal silica influenced the compressive strength property differently with different activator compositions.

  20. Effect of extended morning fasting upon ad libitum lunch intake and associated metabolic and hormonal responses in obese adults

    PubMed Central

    Chowdhury, E A; Richardson, J D; Tsintzas, K; Thompson, D; Betts, J A

    2016-01-01

    Background/Objectives: Breakfast omission is positively associated with obesity and increased risk of disease. However, little is known about the acute effects of extended morning fasting upon subsequent energy intake and associated metabolic/regulatory factors in obese adults. Subjects/Methods: In a randomised cross-over design, 24 obese men (n=8) and women (n=16) extended their overnight fast by omitting breakfast consumption or ingesting a typical carbohydrate-rich breakfast of 2183±393 kJ (521±94 kcal), before an ad libitum pasta lunch 3 h later. Blood samples were obtained throughout the day until 3 h post lunch and analysed for hormones implicated in appetite regulation, along with metabolic outcomes and subjective appetite measures. Results: Lunch intake was unaffected by extended morning fasting (difference=218 kJ, 95% confidence interval −54 kJ, 490 kJ; P=0.1) resulting in lower total intake in the fasting trial (difference=−1964 kJ, 95% confidence interval −1645 kJ, −2281 kJ; P<0.01). Systemic concentrations of peptide tyrosine–tyrosine and leptin were lower during the afternoon following morning fasting (P⩽0.06). Plasma-acylated ghrelin concentrations were also lower following the ad libitum lunch in the fasting trial (P<0.05) but this effect was not apparent for total ghrelin (P⩾0.1). Serum insulin concentrations were greater throughout the afternoon in the fasting trial (P=0.05), with plasma glucose also greater 1 h after lunch (P<0.01). Extended morning fasting did not result in greater appetite ratings after lunch, with some tendency for lower appetite 3 h post lunch (P=0.09). Conclusions: We demonstrate for the first time that, in obese adults, extended morning fasting does not cause compensatory intake during an ad libitum lunch nor does it increase appetite during the afternoon. Morning fasting reduced satiety hormone responses to a subsequent lunch meal but counterintuitively also reduced concentrations of

  1. The role of metals in modulating metalloprotease activity in the AD brain.

    PubMed

    Filiz, Gulay; Price, Katherine A; Caragounis, Aphrodite; Du, Tai; Crouch, Peter J; White, Anthony R

    2008-03-01

    Biometals such as copper and zinc have an important role in Alzheimer's disease (AD). Accumulating evidence indicates that copper homeostasis is altered in AD brain with elevated extracellular and low intracellular copper levels. Studies in animals and cell cultures have suggested that increasing intracellular copper can ameliorate AD-like pathology including amyloid deposition and tau phosphorylation. Modulating copper homeostasis can also improve cognitive function in animal models of AD. Treatments are now being developed that may result in redistribution of copper within the brain. Metal ligands such as clioquinol (CQ), DP-109 or pyrrolidine dithiocarbamate (PDTC) have shown promising results in animal models of AD, however, the actual mode of action in vivo has not been fully determined. We previously reported that CQ-metal complexes were able to increase intracellular copper levels in vitro. This resulted in stimulation of phosphoinositol-3-kinase activity and mitogen activated protein kinases (MAPK). Increased kinase activity resulted in up-regulated matrix metalloprotease (MMP2 and MMP3) activity resulting in enhanced degradation of secreted A beta. These findings are consistent with previous studies reporting metal-mediated activation of MAPKs and MMPs. How this activation occurs is unknown but evidence suggests that copper may be able to activate membrane receptors such as the epidermal growth factor receptor (EGFR) and result in downstream activation of MAPK pathways. This has been supported by studies showing metal-mediated activation of EGFR through ligand-independent processes in a number of cell-types. Our initial studies reveal that copper complexes can in fact activate EGFR. However, further studies are necessary to determine if metal complexes such as CQ-copper induce up-regulation of A beta-degrading MMP activity through this mechanism. Elucidation of this pathway may have important implications for the development of metal ligand based

  2. Obesity, Metabolic Syndrome, and Physical Activity.

    ERIC Educational Resources Information Center

    Yeater, Rachel

    2000-01-01

    Discusses the scope of the problem of obesity in the United States, noting the health risks associated with being overweight or obese (e.g., gallstones, osteoarthritis, sleep apnea, and colon cancer); discussing the association of type-II diabetes mellitus with obesity; examining the effects of exercise on metabolic disease; and looking at…

  3. Microbial thiamin metabolism in the rumen simulating fermenter (RUSITEC): the effect of acidogenic conditions, a high sulfur level and added thiamin.

    PubMed

    Alves de Oliveira, L; Jean-Blain, C; Komisarczuk-Bony, S; Durix, A; Durier, C

    1997-10-01

    The effects of acidogenic conditions, a high S level and the addition of thiamin on the rumen microbial metabolism of thiamin were investigated in vitro in a semi-continuous fermenter (RUSITEC), using a factorial design. Acidogenic conditions were obtained by simultaneously increasing the starch: cellulose ratio and the amount of solid substrate fed, and by decreasing the buffering capacity of the liquid phase of the fermenter. S in the form of sulfate was supplied at two levels, one corresponding to a control amount of S (2 g/kg dietary DM), the second to an excess (5 g/kg DM) which is sufficient to trigger cerebrocortical necrosis (CCN) when used in vivo. Acidogenic conditions decreased the pH of the fermenters, CH4 production and cellulose digestibility, increased the short-chain fatty acid production, but had no effect on thiamin production. The high S level enhanced the production of sulfide considerably, had no effect ont he microbial metabolism of energy and N, and decreased thiamin production (326 v. 266 nmol/d). The added thiamin was rapidly converted into phosphorylated compounds which largely decreased the apparent synthesis of this vitamin by the rumen microflora. The total thiamin flow was increased by added thiamin. In no case was thiaminase activity in the fermenter liquid phase significantly modified. The high level of S induced only a limited decrease of total thiamin flow. Consequently, it is unlikely that the investigated factors could be considered to be high risk factors for the thiamin-dependent CCN. PMID:9389886

  4. Chlamydial metabolism revisited: interspecies metabolic variability and developmental stage-specific physiologic activities.

    PubMed

    Omsland, Anders; Sixt, Barbara Susanne; Horn, Matthias; Hackstadt, Ted

    2014-07-01

    Chlamydiae are a group of obligate intracellular bacteria comprising important human and animal pathogens as well as symbionts of ubiquitous protists. They are characterized by a developmental cycle including two main morphologically and physiologically distinct stages, the replicating reticulate body and the infectious nondividing elementary body. In this review, we reconstruct the history of studies that have led to our current perception of chlamydial physiology, focusing on their energy and central carbon metabolism. We then compare the metabolic capabilities of pathogenic and environmental chlamydiae highlighting interspecies variability among the metabolically more flexible environmental strains. We discuss recent findings suggesting that chlamydiae may not live as energy parasites throughout the developmental cycle and that elementary bodies are not metabolically inert but exhibit metabolic activity under appropriate axenic conditions. The observed host-free metabolic activity of elementary bodies may reflect adequate recapitulation of the intracellular environment, but there is evidence that this activity is biologically relevant and required for extracellular survival and maintenance of infectivity. The recent discoveries call for a reconsideration of chlamydial metabolism and future in-depth analyses to better understand how species- and stage-specific differences in chlamydial physiology may affect virulence, tissue tropism, and host adaptation.

  5. Controlling self-sustained spiking activity by adding or removing one network link

    NASA Astrophysics Data System (ADS)

    Xu, Kesheng; Huang, Wenwen; Li, Baowen; Dhamala, Mukesh; Liu, Zonghua

    2013-06-01

    Being able to control the neuronal spiking activity in specific brain regions is central to a treatment scheme in several brain disorders such as epileptic seizures, mental depression, and Parkinson's diseases. Here, we present an approach for controlling self-sustained oscillations by adding or removing one directed network link in coupled neuronal oscillators, in contrast to previous approaches of adding stimuli or noise. We find that such networks can exhibit a variety of activity patterns such as on-off switch, sustained spikes, and short-term spikes. We derive the condition for a specific link to be the controller of the on-off effect. A qualitative analysis is provided to facilitate the understanding of the mechanism for spiking activity by adding one link. Our findings represent the first report on generating spike activity with the addition of only one directed link to a network and provide a deeper understanding of the microscopic roots of self-sustained spiking.

  6. An efficient synthesis method targeted to marine alkaloids marinacarbolines A-D and their antitumor activities.

    PubMed

    Li, Jun; Tang, Yang; Jin, Hui-Juan; Cui, Yi-Di; Zhang, Li-Juan; Jiang, Tao

    2015-01-01

    Marinacarbolines A-D are a series of marine β-carboline alkaloids isolated from actinomycete Marinactinospora thermotolerans of the deep South China Sea with antiplasmodial activities. In inhibition assays of in vitro growth of Plasmodium falciparum, marinacarbolines exhibited antiplasmodial activity against drug-sensitive line 3D7 and drug-resistant line Dd2 of P. falciparum. However, approaches for the synthesis of such useful compounds are very limited. In this work, we reported a simple, efficient, and versatile process to synthesize marinacarbolines A-D (1-4). On the basis of that, the antitumor activities of marinacarbolines in a structure-dependent manner were allowed to be unveiled.

  7. Physical activity and metabolic syndrome in liver transplant recipients.

    PubMed

    Kallwitz, Eric R; Loy, Veronica; Mettu, Praveen; Von Roenn, Natasha; Berkes, Jamie; Cotler, Scott J

    2013-10-01

    There is a high prevalence of metabolic syndrome in liver transplant recipients, a population that tends to be physically inactive. The aim of this study was to characterize physical activity and evaluate the relationship between physical activity and metabolic syndrome after liver transplantation. A cross-sectional analysis was performed in patients more than 3 months after transplantation. Metabolic syndrome was classified according to National Cholesterol Education Panel Adult Treatment Panel III guidelines. Physical activity, including duration, frequency, and metabolic equivalents of task (METs), was assessed. The study population consisted of 204 subjects, with 156 more than 1 year after transplantation. The median time after transplantation was 53.5 months (range = 3-299 months). The mean duration of exercise was 90 ± 142 minutes, and the mean MET score was 3.6 ± 1.5. Metabolic syndrome was observed in 58.8% of all subjects and in 63.5% of the subjects more than 1 year after transplantation. In a multivariate analysis involving all subjects, metabolic syndrome was associated with a time after transplantation greater than 1 year [odds ratio (OR) = 2.909, 95% confidence interval (CI) = 1.389-6.092] and older age (OR = 1.036, 95% CI = 1.001-1.072). A second analysis was performed for only patients more than 1 year after transplantation. In a multivariate analysis, metabolic syndrome was associated with lower exercise intensity (OR = 0.690, 95% CI = 0.536-0.887), older age (OR = 1.056, 95% CI = 1.014-1.101), and pretransplant diabetes (OR = 4.246, 95% CI = 1.300-13.864). In conclusion, metabolic syndrome is common after liver transplantation, and the rate is significantly higher in patients more than 1 year after transplantation. The observation that exercise intensity is inversely related to metabolic syndrome after transplantation is novel and suggests that physical activity might provide a means for reducing metabolic syndrome complications in liver

  8. Chemoprotective activity of boldine: modulation of drug-metabolizing enzymes.

    PubMed

    Kubínová, R; Machala, M; Minksová, K; Neca, J; Suchý, V

    2001-03-01

    Possible chemoprotective effects of the naturally occurring alkaloid boldine, a major alkaloid of boldo (Peumus boldus Mol.) leaves and bark, including in vitro modulations of drug-metabolizing enzymes in mouse hepatoma Hepa-1 cell line and mouse hepatic microsomes, were investigated. Boldine manifested inhibition activity on hepatic microsomal CYP1A-dependent 7-ethoxyresorufin O-deethylase and CYP3A-dependent testosterone 6 beta-hydroxylase activities and stimulated glutathione S-transferase activity in Hepa-1 cells. In addition to the known antioxidant activity, boldine could decrease the metabolic activation of other xenobiotics including chemical mutagens. PMID:11265593

  9. Metabolic activity, experiment M171. [space flight effects on human metabolism

    NASA Technical Reports Server (NTRS)

    Michel, E. L.; Rummel, J. A.

    1973-01-01

    The Skylab metabolic activity experiment determines if man's metabolic effectiveness in doing mechanical work is progressively altered by a simulated Skylab environment, including environmental factors such as slightly increased pCO2. This test identified several hardware/procedural anomalies. The most important of these were: (1) the metabolic analyzer measured carbon dioxide production and expired water too high; (2) the ergometer load module failed under continuous high workload conditions; (3) a higher than desirable number of erroneous blood pressure measurements were recorded; (4) vital capacity measurements were unreliable; and (5) anticipated crew personal exercise needs to be more structured.

  10. Anatomical Grading for Metabolic Activity of Brown Adipose Tissue

    PubMed Central

    Becker, Anton S.; Nagel, Hannes W.; Wolfrum, Christian; Burger, Irene A.

    2016-01-01

    Background Recent advances in obesity research suggest that BAT activity, or absence thereof, may be an important factor in the growing epidemic of obesity and its manifold complications. It is thus important to assess larger populations for BAT-activating and deactivating factors. 18FDG-PET/CT is the standard method to detect and quantify metabolic BAT activity, however, the manual measurement is not suitable for large studies due to its time-consuming nature and poor reproducibility across different software and devices. Methodology/Main Findings In a retrospective study, 1060 consecutive scans of 1031 patients receiving a diagnostic 18FDG-PET/CT were examined for the presence of active BAT. Patients were classified according to a 3-tier system (supraclavicular, mediastinal, infradiaphragmatic) depending on the anatomical location of their active BAT depots, with the most caudal location being the decisive factor. The metabolic parameters (maximum activity, total volume and total glycolysis) were measured on a standard PET/CT workstation. Mean age of the population was 60±14.6y. 41.61% of patients were female. Metabolically active BAT was found in 53 patients (5.1%). Female, younger and leaner patients tended to have more active BAT, higher metabolic activity and more caudally active BAT. In total, 15 patients showed only supraclavicular, 27 additional mediastinal, and 11 infradiaphragmal activity. Interestingly, the activation of BAT always followed a cranio-caudal gradient. This anatomical pattern correlated with age and BMI as well as with all metabolic parameters, including maximum and total glycolysis (p<0.001). Conclusion Based on our data we propose a simple method to grade or quantify the degree of BAT amount/activity in patients based on the most caudally activated depot. As new modalities for BAT visualization may arise in the future, this system would allow direct comparability with other modalities, in contrary to the PET-metrics, which are

  11. BACE1 activity in cerebrospinal fluid and its relation to markers of AD pathology.

    PubMed

    Mulder, Sandra D; van der Flier, Wiesje M; Verheijen, Jan H; Mulder, Cees; Scheltens, Philip; Blankenstein, Marinus A; Hack, C Erik; Veerhuis, Robert

    2010-01-01

    Several studies have shown that reduced amyloid-beta 1-42 (Abeta(42)) and increased tau levels in cerebrospinal fluid (CSF) reflect increased Alzheimer's disease (AD) pathology in the brain. beta-site APP cleaving enzyme (BACE1) is thought to be the major beta-secretase involved in Abeta production in the brain, and therefore we investigated the relation between BACE1 activity and CSF markers Abeta(40), Abeta(42), total tau (t-tau), and tau phosphorylated at threonine 181 (p-tau) in CSF of control (n=12), mild cognitive impairment (n=18), and AD (n=17) subjects. Patients were classified according to their Abeta(42), t-tau, and p-tau CSF biomarker levels, with either an AD-like biomarker profile (two or three biomarkers abnormal: Abeta(42) < 495 pg/ml in combination with t-tau > 356 pg/ml, and/or p-tau > 54 pg/ml) or a normal biomarker profile (AD-like biomarker profile (66 +/- 6 years, 53% female, and Mini-Mental Status Examination (MMSE) score: 23 +/- 5) and 28 subjects with a normal biomarker profile (62 +/- 11 years, 43% female, and MMSE score: 27 +/- 4). Subjects with an AD-like biomarker profile had higher CSF BACE1 activity levels, compared to patients with a normal biomarker profile (20 pg/ml and 16 pg/ml respectively; p=0.01), when controlled for age and gender. In the whole sample, BACE1 activity correlated with CSF levels of Abeta(40), t-tau, and p-tau (r=0.38, r=0.63, and r=0.65; all p< 0.05), but not with Abeta(42). These data suggest that increased BACE1 activity in CSF relates to AD pathology in the brain.

  12. BACE1 activity in cerebrospinal fluid and its relation to markers of AD pathology.

    PubMed

    Mulder, Sandra D; van der Flier, Wiesje M; Verheijen, Jan H; Mulder, Cees; Scheltens, Philip; Blankenstein, Marinus A; Hack, C Erik; Veerhuis, Robert

    2010-01-01

    Several studies have shown that reduced amyloid-beta 1-42 (Abeta(42)) and increased tau levels in cerebrospinal fluid (CSF) reflect increased Alzheimer's disease (AD) pathology in the brain. beta-site APP cleaving enzyme (BACE1) is thought to be the major beta-secretase involved in Abeta production in the brain, and therefore we investigated the relation between BACE1 activity and CSF markers Abeta(40), Abeta(42), total tau (t-tau), and tau phosphorylated at threonine 181 (p-tau) in CSF of control (n=12), mild cognitive impairment (n=18), and AD (n=17) subjects. Patients were classified according to their Abeta(42), t-tau, and p-tau CSF biomarker levels, with either an AD-like biomarker profile (two or three biomarkers abnormal: Abeta(42) < 495 pg/ml in combination with t-tau > 356 pg/ml, and/or p-tau > 54 pg/ml) or a normal biomarker profile (AD-like biomarker profile (66 +/- 6 years, 53% female, and Mini-Mental Status Examination (MMSE) score: 23 +/- 5) and 28 subjects with a normal biomarker profile (62 +/- 11 years, 43% female, and MMSE score: 27 +/- 4). Subjects with an AD-like biomarker profile had higher CSF BACE1 activity levels, compared to patients with a normal biomarker profile (20 pg/ml and 16 pg/ml respectively; p=0.01), when controlled for age and gender. In the whole sample, BACE1 activity correlated with CSF levels of Abeta(40), t-tau, and p-tau (r=0.38, r=0.63, and r=0.65; all p< 0.05), but not with Abeta(42). These data suggest that increased BACE1 activity in CSF relates to AD pathology in the brain. PMID:20164582

  13. Inuloxins A-D and derivatives as antileishmanial agents: structure-activity relationship study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Inuloxins A-D (1-4) and a-costic acid (5), the phytotoxic compounds previously isolated from Inula viscosa, as well as synthetic derivatives of inuloxin A (compounds 6-10), inuloxin C (compound 11) and inuloxin D (compound 12) were tested in vitro for their activity against Leishmania donovani, the ...

  14. Ethanol Metabolism Activates Cell Cycle Checkpoint Kinase, Chk2

    PubMed Central

    Clemens, Dahn L.; Mahan Schneider, Katrina J.; Nuss, Robert F.

    2011-01-01

    Chronic ethanol abuse results in hepatocyte injury and impairs hepatocyte replication. We have previously shown that ethanol metabolism results in cell cycle arrest at the G2/M transition, which is partially mediated by inhibitory phosphorylation of the cyclin-dependent kinase, Cdc2. To further delineate the mechanisms by which ethanol metabolism mediates this G2/M arrest, we investigated the involvement of upstream regulators of Cdc2 activity. Cdc2 is activated by the phosphatase Cdc25C. The activity of Cdc25C can, in turn, be regulated by the checkpoint kinase, Chk2, which is regulated by the kinase ataxia telangiectasia mutated (ATM). To investigate the involvement of these regulators of Cdc2 activity, VA-13 cells, which are Hep G2 cells modified to efficiently express alcohol dehydrogenase, were cultured in the presence or absence of 25 mM ethanol. Immunoblots were performed to determine the effects of ethanol metabolism on the activation of Cdc25C, Chk2, and ATM. Ethanol metabolism increased the active forms of ATM, and Chk2, as well as the phosphorylated form of Cdc25C. Additionally, inhibition of ATM resulted in approximately 50% of the cells being rescued from the G2/M cell cycle arrest, and ameliorated the inhibitory phosphorylation of Cdc2. Our findings demonstrate that ethanol metabolism activates ATM. ATM can activate the checkpoint kinase Chk2, resulting in phosphorylation of Cdc25C, and ultimately in the accumulation of inactive Cdc2. This may, in part, explain the ethanol metabolism-mediated impairment in hepatocyte replication, which may be important in the initiation and progression of alcoholic liver injury. PMID:21924579

  15. Physical Activity, Metabolic Syndrome, and Overweight in Rural Youth

    ERIC Educational Resources Information Center

    Moore, Justin B.; Davis, Catherine L.; Baxter, Suzanne Domel; Lewis, Richard D.; Yin, Zenong

    2008-01-01

    Background: Research suggests significant health differences between rural dwelling youth and their urban counterparts with relation to cardiovascular risk factors. This study was conducted to (1) determine relationships between physical activity and markers of metabolic syndrome, and (2) to explore factors relating to physical activity in a…

  16. The HOMA-Adiponectin (HOMA-AD) Closely Mirrors the HOMA-IR Index in the Screening of Insulin Resistance in the Brazilian Metabolic Syndrome Study (BRAMS)

    PubMed Central

    Cassani, Roberta Soares Lara; Forti, Adriana Costa e; Pareja, José Carlos; Tambascia, Marcos Antonio; Geloneze, Bruno

    2016-01-01

    Background The major adverse consequences of obesity are associated with the development of insulin resistance (IR) and adiposopathy. The Homeostasis Model Assessment-Adiponectin (HOMA-AD) was proposed as a modified version of the HOMA1-IR, which incorporates adiponectin in the denominator of the index. Objectives To evaluate the performance of the HOMA-AD index compared with the HOMA1-IR index as a surrogate marker of IR in women, and to establish the cutoff value of the HOMA-AD. Subjects/Methods The Brazilian Metabolic Syndrome Study (BRAMS) is a cross-sectional multicenter survey. The data from 1,061 subjects met the desired criteria: 18–65 years old, BMI: 18.5–49.9 Kg/m² and without diabetes. The IR was assessed by the indexes HOMA1-IR and HOMA-AD (total sample) and by the hyperglycemic clamp (n = 49). Metabolic syndrome was defined using the IDF criteria. Results For the IR assessed by the clamp, the HOMA-AD demonstrated a stronger coefficient of correlation (r = -0.64) compared with the HOMA1-IR (r = -0.56); p < 0.0001. In the ROC analysis, compared with the HOMA1-IR, the HOMA-AD showed higher values of the AUC for the identification of IR based on the clamp test (AUC: 0.844 vs. AUC: 0.804) and on the metabolic syndrome (AUC: 0.703 vs. AUC: 0.689), respectively; p < 0.001 for all. However, the pairwise comparison did not show evidence of superiority for the HOMA-AD in comparison with the HOMA1-IR in the diagnosis of IR and metabolic syndrome (p > 0.05). The optimal cutoff identified for the HOMA-AD for the diagnosis of IR was 0.95. Conclusions The HOMA-AD index was demonstrated to be a useful surrogate marker for detecting IR among adult women and presented a similar performance compared with the HOMA1-IR index. These results may assist physicians and researchers in determining which method to use to evaluate IR in light of the available facilities. PMID:27490249

  17. Metabolically Active Glucosides in Oleaceae Seeds

    PubMed Central

    Sondheimer, E.; Blank, G. E.; Galson, Eva C.; Sheets, F. M.

    1970-01-01

    The seeds of six woody species of Oleaceae representing three genera, contain high concentrations of water-soluble glucosides, with major absorption maxima below 240 nanometers. In Fraxinus americana seeds three of these compounds, designated GL-3, GL-5, and GL-6, account for almost 10% of the dry weight. They are found in the endosperm and embryo but not in the pericarp. While the level of GL-5 is not particularly influenced by the physiological state of the embryo, that of GL-3 and GL-6 decreases as a result of germination and growth during a 10-day period. As the concentrations of GL-3 and GL-6 decrease, new ultraviolet-absorbing compounds are formed. The changes in the concentration of the ultraviolet-absorbing glucosides during cold temperature after-ripening, prior to germination, are small. When germination of dormant embryos is induced with gibberellic acid, the concentrations of GL-3 and GL-6 decrease in a manner similar to that observed with nondormant embryos. In the presence of abscisic acid no losses of GL-3 and GL-6 were observed. It is suggested that GL-3 and GL-6 fulfill some definite functions in the germination and growth of F. americana embryos, and that gibberellic acid and abscisic acid can exert a regulatory effect on the metabolism of these glucosides. Images PMID:16657368

  18. The Influence of AD Family History and APOE4 on Mesial Temporal Lobe Activation

    PubMed Central

    Johnson, Sterling C.; Schmitz, Taylor W.; Trivedi, Mehul A.; Ries, Michele L.; Torgerson, Britta M.; Carlsson, Cynthia; Asthana, Sanjay; Hermann, Bruce P.; Sager, Mark A.

    2009-01-01

    First-degree family history of sporadic Alzheimer Disease (AD) and the apolipoprotein E ε4 (APOE4) are risk factors for developing AD. Although the role of APOE4 in AD pathogenesis has been well studied, family history remains a rarely studied and poorly understood risk factor. Both putatively cause early brain changes prior to symptomatic disease, but the relative contribution of each on brain function is unknown. We examined 68 middle-aged participants with a parent diagnosed with AD (+FH) and 64 age- and education-matched controls without a first-degree family history of any dementia (−FH). All underwent cognitive testing, APOE genotyping and a functional MRI (fMRI) encoding task that required discrimination of novel items from previously learned items. A 2 × 2 factorial ANOVA (presence/absence of parental family history and presence/absence of the APOE4) was used to detect group effects. A greater response to novel items was detected in the mesial temporal lobe and fusiform gyrus bilaterally among persons without a first-degree family history of AD. In hippocampal areas, the −FH +ε4 group exhibited the greatest signal change, and the +FH +ε4 group the least. These findings indicate that FH of AD is an important predictor of hippocampal activation during encoding and that FH may modulate the effect of APOE4 in these middle-aged adults, suggesting that an as yet unspecified factor embodied in first-degree family history of AD is influencing the expression of APOE4 on brain function. PMID:16738250

  19. Influence of physical activity to bone metabolism.

    PubMed

    Drenjančević, Ines; Davidović Cvetko, Erna

    2013-02-01

    Bone remodeling is a lifetime process. Peak bone mass is achieved in the twenties, and that value is very important for skeleton health in older years of life. Modern life style with its diet poor in nutrients, and very low intensity of physical activity negatively influences health in general, and bone health as well. Bones are adapting to changes in load, so applying mechanical strain to bones results in greater bone mass and hardness. That makes physical activity important in maintaining skeleton health. Numerous studies confirm good influence of regular exercising to bone health, and connection of physical activity in youth to better bone density in older age. To activate bone remodeling mechanisms, it is necessary to apply mechanical strain to bones by exercise. Considering global problem of bone loss and osteoporosis new ways of activating young people to practice sports and active stile of life are necessary to maintain skeleton health and health in general. This paper aims to review physiological mechanisms of bone remodeling that are influenced by physical exercise. PMID:23348155

  20. Glutamate and GABA-metabolizing enzymes in post-mortem cerebellum in Alzheimer's disease: phosphate-activated glutaminase and glutamic acid decarboxylase.

    PubMed

    Burbaeva, G Sh; Boksha, I S; Tereshkina, E B; Savushkina, O K; Prokhorova, T A; Vorobyeva, E A

    2014-10-01

    Enzymes of glutamate and GABA metabolism in postmortem cerebellum from patients with Alzheimer's disease (AD) have not been comprehensively studied. The present work reports results of original comparative study on levels of phosphate-activated glutaminase (PAG) and glutamic acid decarboxylase isoenzymes (GAD65/67) in autopsied cerebellum samples from AD patients and matched controls (13 cases in each group) as well as summarizes published evidence for altered levels of PAG and GAD65/67 in AD brain. Altered (decreased) levels of these enzymes and changes in links between amounts of these enzymes and other glutamate-metabolizing enzymes (such as glutamate dehydrogenase and glutamine synthetase-like protein) in AD cerebella suggest significantly impaired glutamate and GABA metabolism in this brain region, which was previously regarded as not substantially involved in AD pathogenesis.

  1. Copper oxide nanoparticles inhibit the metabolic activity of Saccharomyces cerevisiae.

    PubMed

    Mashock, Michael J; Kappell, Anthony D; Hallaj, Nadia; Hristova, Krassimira R

    2016-01-01

    Copper oxide nanoparticles (CuO NPs) are used increasingly in industrial applications and consumer products and thus may pose risk to human and environmental health. The interaction of CuO NPs with complex media and the impact on cell metabolism when exposed to sublethal concentrations are largely unknown. In the present study, the short-term effects of 2 different sized manufactured CuO NPs on metabolic activity of Saccharomyces cerevisiae were studied. The role of released Cu(2+) during dissolution of NPs in the growth media and the CuO nanostructure were considered. Characterization showed that the 28 nm and 64 nm CuO NPs used in the present study have different primary diameter, similar hydrodynamic diameter, and significantly different concentrations of dissolved Cu(2+) ions in the growth media released from the same initial NP mass. Exposures to CuO NPs or the released Cu(2+) fraction, at doses that do not have impact on cell viability, showed significant inhibition on S. cerevisiae cellular metabolic activity. A greater CuO NP effect on the metabolic activity of S. cerevisiae growth under respiring conditions was observed. Under the tested conditions the observed metabolic inhibition from the NPs was not explained fully by the released Cu ions from the dissolving NPs.

  2. Effects of activation of endocannabinoid system on myocardial metabolism.

    PubMed

    Polak, Agnieszka; Harasim, Ewa; Chabowski, Adrian

    2016-01-01

    Endocannabinoids exert their effect on the regulation of energy homeostasis via activation of specific receptors. They control food intake, secretion of insulin, lipids and glucose metabolism, lipid storage. Long chain fatty acids are the main myocardial energy substrate. However, the heart exerts enormous metabolic flexibility emphasized by its ability to utilzation not only fatty acids, but also glucose, lactate and ketone bodies. Endocannabinoids can directly act on the cardiomyocytes through the CB1 and CB2 receptors present in cardiomyocytes. It appears that direct activation of CB1 receptors promotes increased lipogenesis, pericardial steatosis and bioelectrical dysfunction of the heart. In contrast, stimulation of CB2 receptors exhibits cardioprotective properties, helping to maintain appropriate amount of ATP in cardiomyocytes. Furthermore, the effects of endocannabinoids at both the central nervous system and peripheral tissues, such as liver, pancreas, or adipose tissue, resulting indirectly in plasma availability of energy substrates and affects myocardial metabolism. To date, there is little evidence that describes effects of activation of the endocannabinoid system in the cardiovascular system under physiological conditions. In the present paper the impact of metabolic diseases, i. e. obesity and diabetes, as well as the cardiovascular diseases - hypertension, myocardial ischemia and myocardial infarction on the deregulation of the endocannabinoid system and its effect on the metabolism are described. PMID:27333924

  3. Fructose induces prothrombotic phenotype in human endothelial cells : A new role for "added sugar" in cardio-metabolic risk.

    PubMed

    Cirillo, Plinio; Pellegrino, Grazia; Conte, Stefano; Maresca, Fabio; Pacifico, Francesco; Leonardi, Antonio; Trimarco, Bruno

    2015-11-01

    Intake of large amounts of added sweeteners has been associated with the pathogenesis of cardiometabolic risk. Several studies have shown that fructose increases the cardiovascular risk by modulating endothelial dysfunction and promoting atherosclerosis. Recently, a potential role for fructose in cardiovascular thrombosis has been suggested but with controversial results. Tissue factor (TF) plays a pivotal role in the pathophysiology of cardiovascular thrombosis by triggering the formation of intracoronary thrombi following endothelial injury. This study investigates the effects of fructose, in a concentration range usually observed in the plasma of patients with increased cardiovascular risk, on TF in human umbilical endothelial cells (HUVECs). Cells were stimulated with increasing concentrations of fructose (0.25, 1 and 2.5 mM) and then processed to evaluate TF-mRNA levels by real-time PCR as well as TF expression/activity by FACS analysis and procoagulant activity. Finally, a potential molecular pathway involved in modulating this phenomenon was investigated. We demonstrate that fructose induces transcription of mRNA for TF. In addition, we show that this monosaccharide promotes surface expression of TF that is functionally active. Fructose effects on TF appear modulated by the oxygen free radicals through activation of the transcription factor NF-κB since superoxide dismutase and NF-κB inhibitors suppressed TF expression. Data of the present study, although in vitro, indicate that fructose, besides promoting atherosclerosis, induces a prothrombotic phenotype in HUVECs, thus indicating one the mechanism(s) by which this sweetener might increase cardiometabolic risk.

  4. Molecular Evidence for Metabolically Active Bacteria in the Atmosphere.

    PubMed

    Klein, Ann M; Bohannan, Brendan J M; Jaffe, Daniel A; Levin, David A; Green, Jessica L

    2016-01-01

    Bacterial metabolisms are responsible for critical chemical transformations in nearly all environments, including oceans, freshwater, and soil. Despite the ubiquity of bacteria in the atmosphere, little is known about the metabolic functioning of atmospheric bacterial communities. To gain a better understanding of the metabolism of bacterial communities in the atmosphere, we used a combined empirical and model-based approach to investigate the structure and composition of potentially active bacterial communities in air sampled at a high elevation research station. We found that the composition of the putatively active bacterial community (assayed via rRNA) differed significantly from the total bacterial community (assayed via rDNA). Rare taxa in the total (rDNA) community were disproportionately active relative to abundant taxa, and members of the order Rhodospirillales had the highest potential for activity. We developed theory to explore the effects of random sampling from the rRNA and rDNA communities on observed differences between the communities. We found that random sampling, particularly in cases where active taxa are rare in the rDNA community, will give rise to observed differences in community composition including the occurrence of "phantom taxa", taxa which are detected in the rRNA community but not the rDNA community. We show that the use of comparative rRNA/rDNA techniques can reveal the structure and composition of the metabolically active portion of bacterial communities. Our observations suggest that metabolically active bacteria exist in the atmosphere and that these communities may be involved in the cycling of organic compounds in the atmosphere.

  5. Molecular Evidence for Metabolically Active Bacteria in the Atmosphere

    PubMed Central

    Klein, Ann M.; Bohannan, Brendan J. M.; Jaffe, Daniel A.; Levin, David A.; Green, Jessica L.

    2016-01-01

    Bacterial metabolisms are responsible for critical chemical transformations in nearly all environments, including oceans, freshwater, and soil. Despite the ubiquity of bacteria in the atmosphere, little is known about the metabolic functioning of atmospheric bacterial communities. To gain a better understanding of the metabolism of bacterial communities in the atmosphere, we used a combined empirical and model-based approach to investigate the structure and composition of potentially active bacterial communities in air sampled at a high elevation research station. We found that the composition of the putatively active bacterial community (assayed via rRNA) differed significantly from the total bacterial community (assayed via rDNA). Rare taxa in the total (rDNA) community were disproportionately active relative to abundant taxa, and members of the order Rhodospirillales had the highest potential for activity. We developed theory to explore the effects of random sampling from the rRNA and rDNA communities on observed differences between the communities. We found that random sampling, particularly in cases where active taxa are rare in the rDNA community, will give rise to observed differences in community composition including the occurrence of “phantom taxa”, taxa which are detected in the rRNA community but not the rDNA community. We show that the use of comparative rRNA/rDNA techniques can reveal the structure and composition of the metabolically active portion of bacterial communities. Our observations suggest that metabolically active bacteria exist in the atmosphere and that these communities may be involved in the cycling of organic compounds in the atmosphere. PMID:27252689

  6. An Optimal CDS Construction Algorithm with Activity Scheduling in Ad Hoc Networks.

    PubMed

    Penumalli, Chakradhar; Palanichamy, Yogesh

    2015-01-01

    A new energy efficient optimal Connected Dominating Set (CDS) algorithm with activity scheduling for mobile ad hoc networks (MANETs) is proposed. This algorithm achieves energy efficiency by minimizing the Broadcast Storm Problem [BSP] and at the same time considering the node's remaining energy. The Connected Dominating Set is widely used as a virtual backbone or spine in mobile ad hoc networks [MANETs] or Wireless Sensor Networks [WSN]. The CDS of a graph representing a network has a significant impact on an efficient design of routing protocol in wireless networks. Here the CDS is a distributed algorithm with activity scheduling based on unit disk graph [UDG]. The node's mobility and residual energy (RE) are considered as parameters in the construction of stable optimal energy efficient CDS. The performance is evaluated at various node densities, various transmission ranges, and mobility rates. The theoretical analysis and simulation results of this algorithm are also presented which yield better results.

  7. Examining the link between framed physical activity ads and behavior among women.

    PubMed

    Berenbaum, Erin; Latimer-Cheung, Amy E

    2014-06-01

    Gain-framed messages are more effective at promoting physical activity than loss-framed messages. However, the mechanism through which this effect occurs is unclear. The current experiment examined the effects of message framing on variables described in the communication behavior change model (McGuire, 1989), as well as the mediating effects of these variables on the message-frame-behavior relationship. Sixty low-to-moderately active women viewed 20 gain- or loss-framed ads and five control ads while their eye movements were recorded via eye tracking. The gain-framed ads attracted greater attention, ps < .05; produced more positive attitudes, p = .06; were better recalled, p < .001; influenced decisions to be active, p = .07; and had an immediate and delayed impact on behavior, ps < .05, compared with the loss-framed messages. Mediation analyses failed to reveal any significant effects. This study demonstrates the effects of framed messages on several outcomes; however, the mechanisms underlying these effects remain unclear.

  8. Neighborly interactions of metabolically-activated astrocytes in vivo.

    PubMed

    Dienel, Gerald A; Cruz, Nancy F

    2003-01-01

    Metabolic responses of brain cells to a stimulus are governed, in part, by their enzymatic specialization and interrelationships with neighboring cells, and local shifts in functional metabolism during brain activation are likely to be influenced by the neurotransmitter system, subcellular compartmentation, and anatomical structure. Selected examples of functional activation illustrate the complexity of metabolic interactions in working brain and of interpretation of changes in brain lactate levels. The major focus of this article is the disproportionately higher metabolism of glucose compared to oxygen in normoxic brain, a phenomenon that occurs during activation in humans and animals. The glucose utilized in excess of oxygen is not fully explained by accumulation of glucose, lactate, or glycogen in brain or by lactate efflux from brain to blood. Thus, any lactate derived from the excess glucose could not have been stoichiometrically exported to and metabolized by neighboring neurons because oxygen consumption would have otherwise increased and matched that of glucose. Metabolic labeling of tricarboxylic acid cycle-derived amino acids increased during brief sensory stimulation, reflecting a rise in oxidative metabolism. Brain glycogen is mainly in astrocytes, and its level falls throughout the stimulus and early post-activation interval. Glycogenolysis cannot be accounted for by lactate accumulation or oxidation; there must be rapid product clearance. Glycogen restoration is slow and diversion of glucose from oxidative pathways for its re-synthesis could reduce the global O(2)/glucose uptake ratio; astrocytes could downshift this ratio for up to an hour after 5 min stimulus. Morphological studies of astrocytes reveal a paucity of cytoplasm and organelles in the fine processes that surround synapses and form gap junction connections with neighboring astrocytes. Specialized regions of astrocytes, e.g. their endfeet and thin peripheral lamellae, are likely to have

  9. AMP-activated protein kinase and metabolic control

    PubMed Central

    Viollet, Benoit; Andreelli, Fabrizio

    2011-01-01

    AMP-activated protein kinase (AMPK), a phylogenetically conserved serine/threonine protein kinase, is a major regulator of cellular and whole-body energy homeostasis that coordinates metabolic pathways in order to balance nutrient supply with energy demand. It is now recognized that pharmacological activation of AMPK improves blood glucose homeostasis, lipid profile and blood pressure in insulin-resistant rodents. Indeed, AMPK activation mimics the beneficial effects of physical activity or those of calorie restriction by acting on multiple cellular targets. In addition it is now demonstrated that AMPK is one of the probable (albeit indirect) targets of major antidiabetic drugs including, the biguanides (metformin) and thiazolidinediones, as well as of insulin sensitizing adipokines (e.g., adiponectin). Taken together, such findings highlight the logic underlying the concept of targeting the AMPK pathway for the treatment of metabolic syndrome and type 2 diabetes. PMID:21484577

  10. Biogeography of Metabolically Active Microbial Populations within the Subseafloor Biosphere

    NASA Astrophysics Data System (ADS)

    Reese, B. K.; Shepard, A.; St. Peter, C.; Mills, H. J.

    2011-12-01

    Microbial life in deep marine sediments is widespread, metabolically active and diverse. Evidence of prokaryotic communities in sediments as deep as 800 m below the seafloor (mbsf) have been found. By recycling carbon and nutrients through biological and geochemical processes, the deep subsurface has the potential to remain metabolically active over geologic time scales. While a vast majority of the subsurface biosphere remains under studied, recent advances in molecular techniques and an increased focus on microbiological sampling during IODP expeditions have provided the initial steps toward better characterizations of the microbial communities. Coupling of geochemistry and RNA-based molecular analysis is essential to the description of the active microbial populations within the subsurface biosphere. Studies based on DNA may describe the taxa and metabolic pathways from the total microbial community within the sediment, whether the cells sampled were metabolically active, quiescent or dead. Due to a short lifespan within a cell, only an RNA-based analysis can be used to identify linkages between active populations and observed geochemistry. This study will coalesce and compare RNA sequence and geochemical data from Expeditions 316 (Nankai Trough), 320 (Pacific Equatorial Age Transect), 325 (Great Barrier Reef) and 329 (South Pacific Gyre) to evaluate the biogeography of microbial lineages actively altering the deep subsurface. The grouping of sediments allows for a wide range of geochemical environments to be compared, including two environments limited in organic carbon. Significant to this study is the use of similar extraction, amplification and simultaneous 454 pyrosequencing on all sediment populations allowing for robust comparisons with similar protocol strengths and biases. Initial trends support previously described reduction of diversity with increasing depth. The co-localization of active reductive and oxidative lineages suggests a potential cryptic

  11. Metabolic activation of 2-methylfuran by rat microsomal systems

    SciTech Connect

    Ravindranath, V.; Boyd, M.R.

    1985-05-01

    2-Methylfuran (2-MF), a constituent of cigarette smoke and coffee, causes necrosis of liver, lungs, and kidneys in rodents. 2-MF is metabolically activated by mixed-function oxidases to acetylacrolein, a reactive metabolite that binds covalently to microsomal protein. The hepatic microsomal metabolism of 2-MF to reactive metabolite required the presence of NADPH and oxygen and was dependent on incubation time and substrate concentration. The microsomal metabolism of 2-MF was inducible by pretreatment of rats with phenobarbital and was inhibited by piperonyl butoxide and N-octyl imidazole, which indicates that the metabolism of 2-MF may be mediated by cytochrome P-450. Acetylacrolein was a potent inhibitor of mixed-function oxidase and completely inhibited the microsomal metabolism of 2-MF, indicating that 2-MF is a suicide substrate for the enzyme. The sulfhydryl nucleophile cysteine was a better trapping agent of the reactive metabolite of 2-MF than N-acetylcysteine or glutathione. Lysine decreased the covalent binding of 2-MF metabolites, presumably by reacting with the aldehyde group of acetylacrolein. In addition, in the presence of NADPH, 2-MF was bioactivated by both pulmonary and renal cortical microsomes to reactive metabolites that were covalently bound to microsomal proteins.

  12. Activating Transcription Factor 3 Regulates Immune and Metabolic Homeostasis

    PubMed Central

    Rynes, Jan; Donohoe, Colin D.; Frommolt, Peter; Brodesser, Susanne; Jindra, Marek

    2012-01-01

    Integration of metabolic and immune responses during animal development ensures energy balance, permitting both growth and defense. Disturbed homeostasis causes organ failure, growth retardation, and metabolic disorders. Here, we show that the Drosophila melanogaster activating transcription factor 3 (Atf3) safeguards metabolic and immune system homeostasis. Loss of Atf3 results in chronic inflammation and starvation responses mounted primarily by the larval gut epithelium, while the fat body suffers lipid overload, causing energy imbalance and death. Hyperactive proinflammatory and stress signaling through NF-κB/Relish, Jun N-terminal kinase, and FOXO in atf3 mutants deregulates genes important for immune defense, digestion, and lipid metabolism. Reducing the dose of either FOXO or Relish normalizes both lipid metabolism and gene expression in atf3 mutants. The function of Atf3 is conserved, as human ATF3 averts some of the Drosophila mutant phenotypes, improving their survival. The single Drosophila Atf3 may incorporate the diversified roles of two related mammalian proteins. PMID:22851689

  13. Dynamic model for selective metabolic activation in chemical carcinogenesis

    SciTech Connect

    Selkirk, J.K.; MacLeod, M.C.

    1980-01-01

    Theoretical calculations predict the relative ease of formation of carbonium ions from 7,8-dihydro-7,8-dihydroxybenzo(a)pyrene-9,10-oxide or from either of the 2 symmetrical bay regions of B(e)P, and suggest their attraction to cellular nucleophiles. When both isomers were metabolized by hamster embryo fibroblasts (HEF) and the products analyzed, the results showed that the probable reason for benzo(e)pyrene's lack of carcinogenicity was its metabolic preference to attack the molecule away from the bay-region area. Particularly striking was the absence of any evidence for the formation of a significant amount of B(e)P-9,10-dihydrodiol. This suggests a metabolic basis for the relative lack of carcinogenic and mutagenic activity of B(e)P. The reason for this is not clear but may be due to physical or chemical factors such as membrane solubility or stereochemical requirements of the active site of the enzyme. The bay-region theory of PAH carcinogenesis predicts that carbonium ion formation from 9,10-dihydro-9,10-dihydroxybenzo(e)pyrene-11, 12-oxide, if formed, would be energetically favorable. Thus, the inability of HEF and microcomes to form B(e)P-9,10-dihydrodiol, the precursor of its potentially highly reactive diol-epoxide, would explain the relative inertness of B(e)P in several biological systems. As the subtle biochemical interactions of the various carcinogen intermediates become clarified, it becomes apparent that susceptibility and resistance to malignant transformation are based on a complex set of both chemical and physical parameters. It is becoming clear that metabolism kinetics, membrane interaction, and the role of nuclear metabolism help dictate the passage of the carcinogen and its reactive intermediates into and through the metabolic machinery of the cell. (ERB)

  14. Cyclotron production of ``very high specific activity'' platinum radiotracers in No Carrier Added form

    NASA Astrophysics Data System (ADS)

    Birattari, C.; Bonardi, M.; Groppi, F.; Gini, L.; Gallorini, M.; Sabbioni, E.; Stroosnijder, M. F.

    2001-12-01

    At the "Radiochemistry Laboratory" of Accelerators and Applied Superconductivity Laboratory, LASA, several production and quality assurance methods for short-lived and high specific activity radionuclides, have been developed. Presently, the irradiations are carried out at the Scanditronix MC40 cyclotron (K=38; p, d, He-4 and He-3) of JRC-Ispra, Italy, of the European Community, while both chemical purity and specific activity determination are carried out at the TRIGA MARK II research reactor of University of Pavia and at LASA itself. In order to optimize the irradiation conditions for platinum radiotracer production, both thin- and thick-target excitation function of natOs(α,xn) nuclear reactions were measured. A very selective radiochemical separation to obtain Pt radiotracers in No Carrier Added form, has been developed. Both real specific activity and chemical purity of radiotracer, have been determined by neutron activation analysis and atomic absorption spectrometry. An Isotopic Dilution Factor (IDF) of the order of 50 is achieved.

  15. Metabolic, autophagic, and mitophagic activities in cancer initiation and progression.

    PubMed

    Hjelmeland, Anita; Zhang, Jianhua

    2016-04-01

    Cancer is a complex disease marked by uncontrolled cell growth and invasion. These processes are driven by the accumulation of genetic and epigenetic alterations that promote cancer initiation and progression. Contributing to genome changes are the regulation of oxidative stress and reactive species-induced damage to molecules and organelles. Redox regulation, metabolic plasticity, autophagy, and mitophagy play important and interactive roles in cancer hallmarks including sustained proliferation, activated invasion, and replicative immortality. However, the impact of these processes can differ depending on the signaling pathways altered in cancer, tumor type, tumor stage, and/or the differentiation state. Here, we highlight some of the representative studies on the impact of oxidative and nitrosative activities, mitochondrial bioenergetics, metabolism, and autophagy and mitophagy in the context of tumorigenesis. We discuss the implications of these processes for cellular activities in cancer for anti-cancer-based therapeutics. PMID:27372165

  16. ArthropodaCyc: a CycADS powered collection of BioCyc databases to analyse and compare metabolism of arthropods.

    PubMed

    Baa-Puyoulet, Patrice; Parisot, Nicolas; Febvay, Gérard; Huerta-Cepas, Jaime; Vellozo, Augusto F; Gabaldón, Toni; Calevro, Federica; Charles, Hubert; Colella, Stefano

    2016-01-01

    Arthropods interact with humans at different levels with highly beneficial roles (e.g. as pollinators), as well as with a negative impact for example as vectors of human or animal diseases, or as agricultural pests. Several arthropod genomes are available at present and many others will be sequenced in the near future in the context of the i5K initiative, offering opportunities for reconstructing, modelling and comparing their metabolic networks. In-depth analysis of these genomic data through metabolism reconstruction is expected to contribute to a better understanding of the biology of arthropods, thereby allowing the development of new strategies to control harmful species. In this context, we present here ArthropodaCyc, a dedicated BioCyc collection of databases using the Cyc annotation database system (CycADS), allowing researchers to perform reliable metabolism comparisons of fully sequenced arthropods genomes. Since the annotation quality is a key factor when performing such global genome comparisons, all proteins from the genomes included in the ArthropodaCyc database were re-annotated using several annotation tools and orthology information. All functional/domain annotation results and their sources were integrated in the databases for user access. Currently, ArthropodaCyc offers a centralized repository of metabolic pathways, protein sequence domains, Gene Ontology annotations as well as evolutionary information for 28 arthropod species. Such database collection allows metabolism analysis both with integrated tools and through extraction of data in formats suitable for systems biology studies.Database URL: http://arthropodacyc.cycadsys.org/.

  17. NOTCH reprograms mitochondrial metabolism for proinflammatory macrophage activation

    PubMed Central

    Xu, Jun; Chi, Feng; Guo, Tongsheng; Punj, Vasu; Lee, W.N. Paul; French, Samuel W.; Tsukamoto, Hidekazu

    2015-01-01

    Metabolic reprogramming is implicated in macrophage activation, but the underlying mechanisms are poorly understood. Here, we demonstrate that the NOTCH1 pathway dictates activation of M1 phenotypes in isolated mouse hepatic macrophages (HMacs) and in a murine macrophage cell line by coupling transcriptional upregulation of M1 genes with metabolic upregulation of mitochondrial oxidative phosphorylation and ROS (mtROS) to augment induction of M1 genes. Enhanced mitochondrial glucose oxidation was achieved by increased recruitment of the NOTCH1 intracellular domain (NICD1) to nuclear and mitochondrial genes that encode respiratory chain components and by NOTCH-dependent induction of pyruvate dehydrogenase phosphatase 1 (Pdp1) expression, pyruvate dehydrogenase activity, and glucose flux to the TCA cycle. As such, inhibition of the NOTCH pathway or Pdp1 knockdown abrogated glucose oxidation, mtROS, and M1 gene expression. Conditional NOTCH1 deficiency in the myeloid lineage attenuated HMac M1 activation and inflammation in a murine model of alcoholic steatohepatitis and markedly reduced lethality following endotoxin-mediated fulminant hepatitis in mice. In vivo monocyte tracking further demonstrated the requirement of NOTCH1 for the migration of blood monocytes into the liver and subsequent M1 differentiation. Together, these results reveal that NOTCH1 promotes reprogramming of mitochondrial metabolism for M1 macrophage activation. PMID:25798621

  18. Novel TPP-riboswitch activators bypass metabolic enzyme dependency

    NASA Astrophysics Data System (ADS)

    Mayer, Günter; Lünse, Christina; Suckling, Colin; Scott, Fraser

    2014-07-01

    Riboswitches are conserved regions within mRNA molecules that bind specific metabolites and regulate gene expression. TPP-riboswitches, which respond to thiamine pyrophosphate (TPP), are involved in the regulation of thiamine metabolism in numerous bacteria. As these regulatory RNAs are often modulating essential biosynthesis pathways they have become increasingly interesting as promising antibacterial targets. Here, we describe thiamine analogs containing a central 1,2,3-triazole group to induce repression of thiM-riboswitch dependent gene expression in different E. coli strains. Additionally, we show that compound activation is dependent on proteins involved in the metabolic pathways of thiamine uptake and synthesis. The most promising molecule, triazolethiamine (TT), shows concentration dependent reporter gene repression that is dependent on the presence of thiamine kinase ThiK, whereas the effect of pyrithiamine (PT), a known TPP-riboswitch modulator, is ThiK independent. We further show that this dependence can be bypassed by triazolethiamine-derivatives that bear phosphate-mimicking moieties. As triazolethiamine reveals superior activity compared to pyrithiamine, it represents a very promising starting point for developing novel antibacterial compounds that target TPP-riboswitches. Riboswitch-targeting compounds engage diverse endogenous mechanisms to attain in vivo activity. These findings are of importance for the understanding of compounds that require metabolic activation to achieve effective riboswitch modulation and they enable the design of novel compound generations that are independent of endogenous activation mechanisms.

  19. Peroxisome proliferator-activated receptors, metabolic syndrome and cardiovascular disease.

    PubMed

    Azhar, Salman

    2010-09-01

    Metabolic syndrome (MetS) is a constellation of risk factors including insulin resistance, central obesity, dyslipidemia and hypertension that markedly increase the risk of Type 2 diabetes (T2DM) and cardiovascular disease (CVD). The peroxisome proliferators-activated receptor (PPAR) isotypes, PPARα, PPARδ/ß and PPARγ are ligand-activated nuclear transcription factors, which modulate the expression of an array of genes that play a central role in regulating glucose, lipid and cholesterol metabolism, where imbalance can lead to obesity, T2DM and CVD. They are also drug targets, and currently, PPARα (fibrates) and PPARγ (thiazolodinediones) agonists are in clinical use for treating dyslipidemia and T2DM, respectively. These metabolic characteristics of the PPARs, coupled with their involvement in metabolic diseases, mean extensive efforts are underway worldwide to develop new and efficacious PPAR-based therapies for the treatment of additional maladies associated with the MetS. This article presents an overview of the functional characteristics of three PPAR isotypes, discusses recent advances in our understanding of the diverse biological actions of PPARs, particularly in the vascular system, and summarizes the developmental status of new single, dual, pan (multiple) and partial PPAR agonists for the clinical management of key components of MetS, T2DM and CVD. It also summarizes the clinical outcomes from various clinical trials aimed at evaluating the atheroprotective actions of currently used fibrates and thiazolodinediones. PMID:20932114

  20. Evaluation of a two-generation reproduction toxicity study adding endpoints to detect endocrine disrupting activity using lindane.

    PubMed

    Matsuura, Ikuo; Saitoh, Tetsuji; Tani, Einosuke; Wako, Yumi; Iwata, Hiroshi; Toyota, Naoto; Ishizuka, Yoshihito; Namiki, Masato; Hoshino, Nobuhito; Tsuchitani, Minoru; Ikeda, Yasuo

    2005-12-01

    A two-generation reproduction toxicity study in rats adding extra endpoints to detect endocrine disrupting activity was conducted using lindane by dietary administration at 0, 10, 60, and 300 ppm, for investigation of its utility. The extra endpoints included anogenital distance (AGD), nipple development, sexual maturation (vaginal opening and preputial separation), estrous cycle, spermatogenesis, sex organ weights, and blood hormone concentrations (thyroid and sex hormones). F1 offspring were examined for emotionality (open field test), motor coordination (rotarod test), as well as learning and memory (pole-climbing test). Hepatic drug-metabolizing enzyme activities were also measured. The results revealed general toxicological effects on parental animals, influence on reproductive function, and altered development of offspring; however, they did not demonstrate any distinct changes in the extra endpoints for detection of endocrine disrupting activity. Adult toxicity was observed in both F0 and F1 animals, including suppressed body weight gain and reduced food consumption in both sexes, and deaths of females at 300 ppm. Convulsions and irritability were observed during the perinatal period in pregnant F1 females given 300 ppm. Pathological examination revealed increased liver weights and centrilobular hepatocellular hypertrophy in both sexes and generations at 10 or 60 ppm and above; in addition, increased kidney weights and increased hyaline droplets in the proximal tubule epithelium, and basophilic renal tubules in males were noted at 10 ppm and above. Pituitary weights were decreased in F0 females and in F1 males and females and adrenal weights were increased in F1 males and females at 300 ppm; however, no histological changes were observed, and manifestations suggesting endocrine disrupting activity related to these changes were lacking. Hypertrophy of the thyroid follicular epithelium in F0 females at 300 ppm and in F1 males at 60 and 300 ppm, and decreases

  1. Active metabolism of thyroid hormone during metamorphosis of amphioxus.

    PubMed

    Paris, Mathilde; Hillenweck, Anne; Bertrand, Stéphanie; Delous, Georges; Escriva, Hector; Zalko, Daniel; Cravedi, Jean-Pierre; Laudet, Vincent

    2010-07-01

    Thyroid hormones (THs), and more precisely the 3,3',5-triiodo-l-thyronine (T(3)) acetic derivative 3,3',5-triiodothyroacetic acid (TRIAC), have been shown to activate metamorphosis in amphioxus. However, it remains unknown whether TRIAC is endogenously synthesized in amphioxus and more generally whether an active TH metabolism is regulating metamorphosis. Here we show that amphioxus naturally produces TRIAC from its precursors T(3) and l-thyroxine (T(4)), supporting its possible role as the active TH in amphioxus larvae. In addition, we show that blocking TH production inhibits metamorphosis and that this effect is compensated by exogenous T(3), suggesting that a peak of TH production is important for advancement of proper metamorphosis. Moreover, several amphioxus genes encoding proteins previously proposed to be involved in the TH signaling pathway display expression profiles correlated with metamorphosis. In particular, thyroid hormone receptor (TR) and deiodinases gene expressions are either up- or down-regulated during metamorphosis and by TH treatments. Overall, these results suggest that an active TH metabolism controls metamorphosis in amphioxus, and that endogenous TH production and metabolism as well as TH-regulated metamorphosis are ancestral in the chordate lineage.

  2. Marine Omega-3 Phospholipids: Metabolism and Biological Activities

    PubMed Central

    Burri, Lena; Hoem, Nils; Banni, Sebastiano; Berge, Kjetil

    2012-01-01

    The biological activities of omega-3 fatty acids (n-3 FAs) have been under extensive study for several decades. However, not much attention has been paid to differences of dietary forms, such as triglycerides (TGs) versus ethyl esters or phospholipids (PLs). New innovative marine raw materials, like krill and fish by-products, present n-3 FAs mainly in the PL form. With their increasing availability, new evidence has emerged on n-3 PL biological activities and differences to n-3 TGs. In this review, we describe the recently discovered nutritional properties of n-3 PLs on different parameters of metabolic syndrome and highlight their different metabolic bioavailability in comparison to other dietary forms of n-3 FAs. PMID:23203133

  3. [An electrochemical method for measuring metabolic activity and counting cells].

    PubMed

    Kuznetsov, B a; Khlupova, M e; Shleev, S V; Kaprel'iants, A S; Iaropolov, A I

    2006-01-01

    An express electrochemical method for determining the metabolic activity of live cells based on the possibility of an electron exchange between an electrode and elements of the biological electron transfer chain in the presence of a mediator is proposed. This method is useful for studying any live cells (animal, plant, and microbial), including anaerobic, dormant, and spore cells. The sample preparation and measurement itself does not take more than 30 min. The detection limit in a volume of 15 ml amounts to 10-5 cells/ml. The applicability of the assessment method of the metabolic activity level during the transition of the bacteria Mycobacterium smegmatis into an uncultivable dormant state was demonstrated. This method is of special value for medicine and environmental control, detecting latent forms of pathogens. An optimal combination of the methods for the express analysis of latent pathogens is proposed. PMID:17066962

  4. Activating and Elucidating Metabolism of Complex Sugars in Yarrowia lipolytica

    PubMed Central

    Ryu, Seunghyun; Hipp, Julie

    2015-01-01

    The oleaginous yeast Yarrowia lipolytica is an industrially important host for production of organic acids, oleochemicals, lipids, and proteins with broad biotechnological applications. Albeit known for decades, the unique native metabolism of Y. lipolytica for using complex fermentable sugars, which are abundant in lignocellulosic biomass, is poorly understood. In this study, we activated and elucidated the native sugar metabolism in Y. lipolytica for cell growth on xylose and cellobiose as well as their mixtures with glucose through comprehensive metabolic and transcriptomic analyses. We identified 7 putative glucose-specific transporters, 16 putative xylose-specific transporters, and 4 putative cellobiose-specific transporters that are transcriptionally upregulated for growth on respective single sugars. Y. lipolytica is capable of using xylose as a carbon source, but xylose dehydrogenase is the key bottleneck of xylose assimilation and is transcriptionally repressed by glucose. Y. lipolytica has a set of 5 extracellular and 6 intracellular β-glucosidases and is capable of assimilating cellobiose via extra- and intracellular mechanisms, the latter being dominant for growth on cellobiose as a sole carbon source. Strikingly, Y. lipolytica exhibited enhanced sugar utilization for growth in mixed sugars, with strong carbon catabolite activation for growth on the mixture of xylose and cellobiose and with mild carbon catabolite repression of glucose on xylose and cellobiose. The results of this study shed light on fundamental understanding of the complex native sugar metabolism of Y. lipolytica and will help guide inverse metabolic engineering of Y. lipolytica for enhanced conversion of biomass-derived fermentable sugars to chemicals and fuels. PMID:26682853

  5. Activating and Elucidating Metabolism of Complex Sugars in Yarrowia lipolytica.

    PubMed

    Ryu, Seunghyun; Hipp, Julie; Trinh, Cong T

    2016-02-01

    The oleaginous yeast Yarrowia lipolytica is an industrially important host for production of organic acids, oleochemicals, lipids, and proteins with broad biotechnological applications. Albeit known for decades, the unique native metabolism of Y. lipolytica for using complex fermentable sugars, which are abundant in lignocellulosic biomass, is poorly understood. In this study, we activated and elucidated the native sugar metabolism in Y. lipolytica for cell growth on xylose and cellobiose as well as their mixtures with glucose through comprehensive metabolic and transcriptomic analyses. We identified 7 putative glucose-specific transporters, 16 putative xylose-specific transporters, and 4 putative cellobiose-specific transporters that are transcriptionally upregulated for growth on respective single sugars. Y. lipolytica is capable of using xylose as a carbon source, but xylose dehydrogenase is the key bottleneck of xylose assimilation and is transcriptionally repressed by glucose. Y. lipolytica has a set of 5 extracellular and 6 intracellular β-glucosidases and is capable of assimilating cellobiose via extra- and intracellular mechanisms, the latter being dominant for growth on cellobiose as a sole carbon source. Strikingly, Y. lipolytica exhibited enhanced sugar utilization for growth in mixed sugars, with strong carbon catabolite activation for growth on the mixture of xylose and cellobiose and with mild carbon catabolite repression of glucose on xylose and cellobiose. The results of this study shed light on fundamental understanding of the complex native sugar metabolism of Y. lipolytica and will help guide inverse metabolic engineering of Y. lipolytica for enhanced conversion of biomass-derived fermentable sugars to chemicals and fuels. PMID:26682853

  6. Heightened hurricane activity on the Little Bahama Bank from 1350 to 1650 AD

    NASA Astrophysics Data System (ADS)

    van Hengstum, Peter J.; Donnelly, Jeffrey P.; Toomey, Michael R.; Albury, Nancy A.; Lane, Philip; Kakuk, Brian

    2014-09-01

    Deciphering how the climate system has controlled North Atlantic tropical cyclone activity through the Holocene will require a larger observational network of prehistoric hurricane activity. Problematically, the tropical North Atlantic is dominated by carbonate landscapes that typically preserve poorer quality coastal sediment records in comparison to their temperate-region counterparts (e.g., sedimentation continuity and rate). Coastal karst basins (CKBs), such as sinkholes, blueholes, and underwater caves, are widely distributed on carbonate platforms and contain overlooked sedimentary records. Here we present a millennium of hurricane deposits on the Little Bahama Bank archived in a 165 cm core that was extracted from 69 m below sea level in a bluehole on Great Abaco Island, The Bahamas. The coarse-grained overwash deposits associated with both hurricanes Jeanne (2004) and Floyd (1999) were identified using radioisotopes (137Cs, 14C, 210Pb), and indicate that the bluehole is sensitive to hurricane-induced sedimentation. Over the last millennium, the Little Bahama Bank experienced heightened hurricane activity from 1350 to 1650 AD. The simplest explanation for this active interval is that favorable climate conditions (El Niño, West African Monsoon, and sea surface temperatures) encouraged North Atlantic hurricane activity at that time. However, asynchronous hurricane activity at similar latitudes in the North Atlantic and Gulf of Mexico suggest that regional oceanography has modulated or amplified regional hurricane activity over the last millennium.

  7. Metabolic activation of carcinogenic ethylbenzene leads to oxidative DNA damage.

    PubMed

    Midorikawa, Kaoru; Uchida, Takafumi; Okamoto, Yoshinori; Toda, Chitose; Sakai, Yoshie; Ueda, Koji; Hiraku, Yusuke; Murata, Mariko; Kawanishi, Shosuke; Kojima, Nakao

    2004-12-01

    Ethylbenzene is carcinogenic to rats and mice, while it has no mutagenic activity. We have investigated whether ethylbenzene undergoes metabolic activation, leading to DNA damage. Ethylbenzene was metabolized to 1-phenylethanol, acetophenone, 2-ethylphenol and 4-ethylphenol by rat liver microsomes. Furthermore, 2-ethylphenol and 4-ethylphenol were metabolically transformed to ring-dihydroxylated metabolites such as ethylhydroquinone and 4-ethylcatechol, respectively. Experiment with 32P-labeled DNA fragment revealed that both ethylhydroquinone and 4-ethylcatechol caused DNA damage in the presence of Cu(II). These dihydroxylated compounds also induced the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine in calf thymus DNA in the presence of Cu(II). Catalase, methional and Cu(I)-specific chelator, bathocuproine, significantly (P<0.05) inhibited oxidative DNA damage, whereas free hydroxyl radical scavenger and superoxide dismutase did not. These results suggest that Cu(I) and H2O2 produced via oxidation of ethylhydroquinone and 4-ethylcatechol are involved in oxidative DNA damage. Addition of an endogenous reductant NADH dramatically enhanced 4-ethylcatechol-induced oxidative DNA damage, whereas ethylhydroquinone-induced DNA damage was slightly enhanced. Enhancing effect of NADH on oxidative DNA damage by 4-ethylcatechol may be explained by assuming that reactive species are generated from the redox cycle. In conclusion, these active dihydroxylated metabolites would be involved in the mechanism of carcinogenesis by ethylbenzene. PMID:15560893

  8. Carbohydrate-active enzymes exemplify entropic principles in metabolism

    PubMed Central

    Kartal, Önder; Mahlow, Sebastian; Skupin, Alexander; Ebenhöh, Oliver

    2011-01-01

    Glycans comprise ubiquitous and essential biopolymers, which usually occur as highly diverse mixtures. The myriad different structures are generated by a limited number of carbohydrate-active enzymes (CAZymes), which are unusual in that they catalyze multiple reactions by being relatively unspecific with respect to substrate size. Existing experimental and theoretical descriptions of CAZyme-mediated reaction systems neither comprehensively explain observed action patterns nor suggest biological functions of polydisperse pools in metabolism. Here, we overcome these limitations with a novel theoretical description of this important class of biological systems in which the mixing entropy of polydisperse pools emerges as an important system variable. In vitro assays of three CAZymes essential for central carbon metabolism confirm the power of our approach to predict equilibrium distributions and non-equilibrium dynamics. A computational study of the turnover of the soluble heteroglycan pool exemplifies how entropy-driven reactions establish a metabolic buffer in vivo that attenuates fluctuations in carbohydrate availability. We argue that this interplay between energy- and entropy-driven processes represents an important regulatory design principle of metabolic systems. PMID:22027553

  9. Metabolically activated steviol, the aglycone of stevioside, is mutagenic.

    PubMed Central

    Pezzuto, J M; Compadre, C M; Swanson, S M; Nanayakkara, D; Kinghorn, A D

    1985-01-01

    Stevioside, a constituent of Stevia rebaudiana, is commonly used as a noncaloric sugar substitute in Japan. Consistent with reports in the literature, we have found that stevioside is not mutagenic as judged by utilization of Salmonella typhimurium strain TM677, either in the presence or in the absence of a metabolic activating system. Similar negative results were obtained with several structurally related sweet-tasting glycosides. However, steviol, the aglycone of stevioside, was found to be highly mutagenic when evaluated in the presence of a 9000 X g supernatant fraction derived from the livers of Aroclor 1254-pretreated rats. Expression of mutagenic activity was dependent on both pretreatment of the rats with Aroclor 1254 and addition of NADPH; unmetabolized steviol was not active. The structurally related species, isosteviol, was not active regardless of metabolic activation. Similarly, chemical reduction of the unsaturated bond linking the carbon-16 and -17 positions of steviol resulted in the generation of two isomeric products, dihydrosteviol A and B, that were not mutagenic. In addition, ent-kaurenoic acid was found to be inactive. It is therefore clear that a metabolite of an integral component of stevioside is mutagenic; structural features of requisite importance for the expression of mutagenic activity include a hydroxy group at position 13 and an unsaturated bond joining the carbon atoms at positions 16 and 17. A potential metabolite of steviol, steviol-16 alpha,17-epoxide, was synthesized chemically and found to be ineffective as a direct-acting mutagen. Thus, although stevioside itself appears innocuous, it would seem prudent to expeditiously and unequivocally establish the human metabolic disposition of this substance. PMID:3887402

  10. Changes to coral health and metabolic activity under oxygen deprivation.

    PubMed

    Murphy, James W A; Richmond, Robert H

    2016-01-01

    On Hawaiian reefs, the fast-growing, invasive algae Gracilaria salicornia overgrows coral heads, restricting water flow and light, thereby smothering corals. Field data shows hypoxic conditions (dissolved oxygen (DO2) < 2 mg/L) occurring underneath algal mats at night, and concurrent bleaching and partial tissue loss of shaded corals. To analyze the impact of nighttime oxygen-deprivation on coral health, this study evaluated changes in coral metabolism through the exposure of corals to chronic hypoxic conditions and subsequent analyses of lactate, octopine, alanopine, and strombine dehydrogenase activities, critical enzymes employed through anaerobic respiration. Following treatments, lactate and octopine dehydrogenase activities were found to have no significant response in activities with treatment and time. However, corals subjected to chronic nighttime hypoxia were found to exhibit significant increases in alanopine dehydrogenase activity after three days of exposure and strombine dehydrogenase activity starting after one overnight exposure cycle. These findings provide new insights into coral metabolic shifts in extremely low-oxygen environments and point to ADH and SDH assays as tools for quantifying the impact of hypoxia on coral health. PMID:27114888

  11. Changes to coral health and metabolic activity under oxygen deprivation

    PubMed Central

    Richmond, Robert H.

    2016-01-01

    On Hawaiian reefs, the fast-growing, invasive algae Gracilaria salicornia overgrows coral heads, restricting water flow and light, thereby smothering corals. Field data shows hypoxic conditions (dissolved oxygen (DO2) < 2 mg/L) occurring underneath algal mats at night, and concurrent bleaching and partial tissue loss of shaded corals. To analyze the impact of nighttime oxygen-deprivation on coral health, this study evaluated changes in coral metabolism through the exposure of corals to chronic hypoxic conditions and subsequent analyses of lactate, octopine, alanopine, and strombine dehydrogenase activities, critical enzymes employed through anaerobic respiration. Following treatments, lactate and octopine dehydrogenase activities were found to have no significant response in activities with treatment and time. However, corals subjected to chronic nighttime hypoxia were found to exhibit significant increases in alanopine dehydrogenase activity after three days of exposure and strombine dehydrogenase activity starting after one overnight exposure cycle. These findings provide new insights into coral metabolic shifts in extremely low-oxygen environments and point to ADH and SDH assays as tools for quantifying the impact of hypoxia on coral health. PMID:27114888

  12. Changes to coral health and metabolic activity under oxygen deprivation.

    PubMed

    Murphy, James W A; Richmond, Robert H

    2016-01-01

    On Hawaiian reefs, the fast-growing, invasive algae Gracilaria salicornia overgrows coral heads, restricting water flow and light, thereby smothering corals. Field data shows hypoxic conditions (dissolved oxygen (DO2) < 2 mg/L) occurring underneath algal mats at night, and concurrent bleaching and partial tissue loss of shaded corals. To analyze the impact of nighttime oxygen-deprivation on coral health, this study evaluated changes in coral metabolism through the exposure of corals to chronic hypoxic conditions and subsequent analyses of lactate, octopine, alanopine, and strombine dehydrogenase activities, critical enzymes employed through anaerobic respiration. Following treatments, lactate and octopine dehydrogenase activities were found to have no significant response in activities with treatment and time. However, corals subjected to chronic nighttime hypoxia were found to exhibit significant increases in alanopine dehydrogenase activity after three days of exposure and strombine dehydrogenase activity starting after one overnight exposure cycle. These findings provide new insights into coral metabolic shifts in extremely low-oxygen environments and point to ADH and SDH assays as tools for quantifying the impact of hypoxia on coral health.

  13. Influence of metabolism on endocrine activities of bisphenol S.

    PubMed

    Skledar, Darja Gramec; Schmidt, Jan; Fic, Anja; Klopčič, Ivana; Trontelj, Jurij; Dolenc, Marija Sollner; Finel, Moshe; Mašič, Lucija Peterlin

    2016-08-01

    Bisphenol S (BPS; bis[4-hydroxyphenyl]sulfone) is commonly used as a replacement for bisphenol A in numerous consumer products. The main goal of this study was to examine the influence of different metabolic reactions that BPS undergoes on the endocrine activity. We demonstrate that hydroxylation of the aromatic ring of BPS, catalyzed mainly by the cytochrome P450 enzymes CYP3A4 and CYP2C9, is its major in-vitro phase I biotransformation. Nevertheless, coupled oxidative-conjugative reactions analyses revealed that glucuronidation and formation of BPS glucuronide is the predominant BPS metabolic pathway. BPS reactive metabolites that can be tracked as glutathione conjugates were not detected in the present study. Two in-vitro systems were used to evaluate the endocrine activity of BPS and its two main metabolites, BPS glucuronide and hydroxylated BPS 4-(4-hydroxy-benzenesulfonyl)-benzene-1,2-diol (BPSM1). In addition, we have tested two structural analogs of BPS, bis[4-(2-hydroxyetoxy)phenyl]sulfone (BHEPS) and 4,4-sulfonylbis(2-methylphenol) (dBPS). The test systems were yeast cells, for evaluating estrogenic and androgenic activities, and the GH3.TRE-Luc reporter cell line for measuring thyroid hormone activity. BPS and BPSM1 were weak agonists of the estrogen receptor, EC50 values of 8.4 × 10(-5) M and 6.7 × 10(-4) M, respectively. Additionally, BPSM1 exhibited weak antagonistic activity toward the thyroid hormone receptor, with an IC50 of 4.3 × 10(-5) M. In contrast to BPSM1, BPS glucuronide was inactive in these assays, inhibiting neither the estrogen nor the thyroid hormone receptors. Hence, glucuronidation appears to be the most important pathway for both BPS metabolism and detoxification.

  14. Sampling and major element chemistry of the recent (A.D. 1631-1944) Vesuvius activity

    USGS Publications Warehouse

    Belkin, H.E.; Kilburn, C.R.J.; de Vivo, B.

    1993-01-01

    Detailed sampling of the Vesuvius lavas erupted in the period A.D. 1631-1944 provides a suite of samples for comprehensive chemical analyses and related studies. Major elements (Si, Ti, Al, Fetotal, Mn, Mg, Ca, Na, K and P), volatile species (Cl, F, S, H2O+, H2O- and CO2), and ferrous iron (Fe2+) were determined for one hundred and forty-nine lavas and five tephra from the A.D. 1631-1944 Vesuvius activity. The lavas represent a relatively homogeneous suite with respect to SiO2, TiO2, FeOtotal, MnO and P2O5, but show systematic variations among MgO, K2O, Na2O, Al2O3 and CaO. The average SiO2 content is 48.0 wt.% and the rocks are classified as tephriphonolites according to their content of alkalis. All of the lavas are silica-undersaturated and are nepheline, leucite, and olivine normative. There is no systematic variation in major-element composition with time, over the period A.D. 1631-1944. The inter-eruption and intra-eruption compositional differences are the same magnitude. The lavas are highly porphyritic with clinopyroxene and leucite as the major phases. Fractionation effects are not reflected in the silica content of the lavas. The variability of MgO, K2O, Na2O, and CaO can be modelled as a relative depletion or accumulation of clinopyroxene. ?? 1993.

  15. Metabolic, anabolic, and mitogenic insulin responses: A tissue-specific perspective for insulin receptor activators

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Insulin acts as the major regulator of the fasting-to-fed metabolic transition by altering substrate metabolism, promoting energy storage, and helping activate protein synthesis. In addition to its glucoregulatory and other metabolic properties, insulin can also act as a growth factor. The metabolic...

  16. Metabolic activities of Lactobacillus spp. strains isolated from kefir.

    PubMed

    Yüksekdag, Zehra Nur; Beyath, Yavuz; Aslim, Belma

    2004-06-01

    A total of 21 strains of Lactobacillus species were isolated from Turkish kefir samples, in order to select the most suitable strains according to their metabolic activities including probiotic properties. As a result of the identification tests, 21 Lactobacillus isolates were identified as L. acidophilus (4%), L. helveticus (9%), L. brevis (9%), L. bulgaricus (14%), L. plantarum (14%), L. casei (19%) and L. lactis (28%). The amount of produced lactic acid, hydrogen peroxide, proteolytic activity, and acetaldehyde productions of Lactobacillus spp. were determined. Different amounts of lactic acid were produced by strains studies; however, lactic acid levels were 1.7-11.4 mg/mL. All strains produced hydrogen peroxide. L. bulgaricus Z14L strain showed no proteolytic activity, L. casei Z6L strain produced the maximum amount (0.16 mg/mL) of proteolytic activity. Acetaldehyde concentration produced in Lactobacillus strains ranged between 0.88-3.52 microg/mL.

  17. ArthropodaCyc: a CycADS powered collection of BioCyc databases to analyse and compare metabolism of arthropods.

    PubMed

    Baa-Puyoulet, Patrice; Parisot, Nicolas; Febvay, Gérard; Huerta-Cepas, Jaime; Vellozo, Augusto F; Gabaldón, Toni; Calevro, Federica; Charles, Hubert; Colella, Stefano

    2016-01-01

    Arthropods interact with humans at different levels with highly beneficial roles (e.g. as pollinators), as well as with a negative impact for example as vectors of human or animal diseases, or as agricultural pests. Several arthropod genomes are available at present and many others will be sequenced in the near future in the context of the i5K initiative, offering opportunities for reconstructing, modelling and comparing their metabolic networks. In-depth analysis of these genomic data through metabolism reconstruction is expected to contribute to a better understanding of the biology of arthropods, thereby allowing the development of new strategies to control harmful species. In this context, we present here ArthropodaCyc, a dedicated BioCyc collection of databases using the Cyc annotation database system (CycADS), allowing researchers to perform reliable metabolism comparisons of fully sequenced arthropods genomes. Since the annotation quality is a key factor when performing such global genome comparisons, all proteins from the genomes included in the ArthropodaCyc database were re-annotated using several annotation tools and orthology information. All functional/domain annotation results and their sources were integrated in the databases for user access. Currently, ArthropodaCyc offers a centralized repository of metabolic pathways, protein sequence domains, Gene Ontology annotations as well as evolutionary information for 28 arthropod species. Such database collection allows metabolism analysis both with integrated tools and through extraction of data in formats suitable for systems biology studies.Database URL: http://arthropodacyc.cycadsys.org/. PMID:27242037

  18. Moonlighting transcriptional activation function of a fungal sulfur metabolism enzyme.

    PubMed

    Levati, Elisabetta; Sartini, Sara; Bolchi, Angelo; Ottonello, Simone; Montanini, Barbara

    2016-01-01

    Moonlighting proteins, including metabolic enzymes acting as transcription factors (TF), are present in a variety of organisms but have not been described in higher fungi so far. In a previous genome-wide analysis of the TF repertoire of the plant-symbiotic fungus Tuber melanosporum, we identified various enzymes, including the sulfur-assimilation enzyme phosphoadenosine-phosphosulfate reductase (PAPS-red), as potential transcriptional activators. A functional analysis performed in the yeast Saccharomyces cerevisiae, now demonstrates that a specific variant of this enzyme, PAPS-red A, localizes to the nucleus and is capable of transcriptional activation. TF moonlighting, which is not present in the other enzyme variant (PAPS-red B) encoded by the T. melanosporum genome, relies on a transplantable C-terminal polypeptide containing an alternating hydrophobic/hydrophilic amino acid motif. A similar moonlighting activity was demonstrated for six additional proteins, suggesting that multitasking is a relatively frequent event. PAPS-red A is sulfur-state-responsive and highly expressed, especially in fruitbodies, and likely acts as a recruiter of transcription components involved in S-metabolism gene network activation. PAPS-red B, instead, is expressed at low levels and localizes to a highly methylated and silenced region of the genome, hinting at an evolutionary mechanism based on gene duplication, followed by epigenetic silencing of this non-moonlighting gene variant. PMID:27121330

  19. Moonlighting transcriptional activation function of a fungal sulfur metabolism enzyme

    PubMed Central

    Levati, Elisabetta; Sartini, Sara; Bolchi, Angelo; Ottonello, Simone; Montanini, Barbara

    2016-01-01

    Moonlighting proteins, including metabolic enzymes acting as transcription factors (TF), are present in a variety of organisms but have not been described in higher fungi so far. In a previous genome-wide analysis of the TF repertoire of the plant-symbiotic fungus Tuber melanosporum, we identified various enzymes, including the sulfur-assimilation enzyme phosphoadenosine-phosphosulfate reductase (PAPS-red), as potential transcriptional activators. A functional analysis performed in the yeast Saccharomyces cerevisiae, now demonstrates that a specific variant of this enzyme, PAPS-red A, localizes to the nucleus and is capable of transcriptional activation. TF moonlighting, which is not present in the other enzyme variant (PAPS-red B) encoded by the T. melanosporum genome, relies on a transplantable C-terminal polypeptide containing an alternating hydrophobic/hydrophilic amino acid motif. A similar moonlighting activity was demonstrated for six additional proteins, suggesting that multitasking is a relatively frequent event. PAPS-red A is sulfur-state-responsive and highly expressed, especially in fruitbodies, and likely acts as a recruiter of transcription components involved in S-metabolism gene network activation. PAPS-red B, instead, is expressed at low levels and localizes to a highly methylated and silenced region of the genome, hinting at an evolutionary mechanism based on gene duplication, followed by epigenetic silencing of this non-moonlighting gene variant. PMID:27121330

  20. Metatranscriptome Analysis of Aquifer Samples Reveals Unexpected Metabolic Lifestyles Relevant to Active Biogeochemical Cycling

    NASA Astrophysics Data System (ADS)

    Beller, H. R.; Jewell, T. N. M.; Karaoz, U.; Banfield, J. F.; Brodie, E.; Williams, K. H.

    2015-12-01

    Modern molecular ecology techniques are revealing the metabolic potential of uncultivated microorganisms, but there is still much to be learned about the actual biogeochemical roles of microbes that have cultivated relatives. Here, we present metatranscriptomic and metagenomic data from a field study that provides evidence of coupled redox processes that have not been documented in cultivated relatives and, indeed, represent strains with metabolic traits that are novel with respect to closely related isolates. The data come from omics analysis of groundwater samples collected during an experiment in which nitrate (a native electron acceptor) was injected into a perennially suboxic aquifer in Rifle (CO). Transcriptional data indicated that just two groups of chemolithoautotrophic bacteria accounted for a very large portion (~80%) of overall community gene expression: (1) members of the Fe(II)-oxidizing Gallionellaceae family and (2) strains of the S-oxidizing species, Sulfurimonas denitrificans. Metabolic lifestyles for Gallionellaceae strains that were novel compared to cultivated representatives included nitrate-dependent Fe(II) oxidation and S oxidation. Evidence for these metabolisms included highly correlated temporal expression in binned data of nitrate reductase (e.g., narGHI) genes (which have never been reported in Gallionellaceae genomes) and Fe(II) oxidation genes (e.g., mtoA) or S oxidation genes (e.g., dsrE, aprA). Of the two most active strains of S. denitrificans, only one showed strong expression of S oxidation genes, whereas the other was apparently using an unexpected (as-yet unidentified) primary electron donor. Transcriptional data added considerable interpretive value to this study, as (1) metagenomic data would not have highlighted these organisms, which had a disproportionately large role in community metabolism relative to their populations, and (2) co-expression of coupled pathway genes could not be predicted based solely on metagenomic data.

  1. A Glutathione S-Transferase with Activity towards cis-1,2-Dichloroepoxyethane Is Involved in Isoprene Utilization by Rhodococcus sp. Strain AD45

    PubMed Central

    van Hylckama Vlieg, Johan E. T.; Kingma, Jaap; van den Wijngaard, Arjan J.; Janssen, Dick B.

    1998-01-01

    Rhodococcus sp. strain AD45 was isolated from an enrichment culture on isoprene (2-methyl-1,3-butadiene). Isoprene-grown cells of strain AD45 oxidized isoprene to 3,4-epoxy-3-methyl-1-butene, cis-1,2-dichloroethene to cis-1,2-dichloroepoxyethane, and trans-1,2-dichloroethene to trans-1,2-dichloroepoxyethane. Isoprene-grown cells also degraded cis-1,2-dichloroepoxyethane and trans-1,2-dichloroepoxyethane. All organic chlorine was liberated as chloride during degradation of cis-1,2-dichloroepoxyethane. A glutathione (GSH)-dependent activity towards 3,4-epoxy-3-methyl-1-butene, epoxypropane, cis-1,2-dichloroepoxyethane, and trans-1,2-dichloroepoxyethane was detected in cell extracts of cultures grown on isoprene and 3,4-epoxy-3-methyl-1-butene. The epoxide-degrading activity of strain AD45 was irreversibly lost upon incubation of cells with 1,2-epoxyhexane. A conjugate of GSH and 1,2-epoxyhexane was detected in cell extracts of cells exposed to 1,2-epoxyhexane, indicating that GSH is the physiological cofactor of the epoxide-transforming activity. The results indicate that a GSH S-transferase is involved in the metabolism of isoprene and that the enzyme can detoxify reactive epoxides produced by monooxygenation of chlorinated ethenes. PMID:9687433

  2. Metabolic transistor strategy for controlling electron transfer chain activity in Escherichia coli.

    PubMed

    Wu, Hui; Tuli, Leepika; Bennett, George N; San, Ka-Yiu

    2015-03-01

    A novel strategy to finely control a large metabolic flux by using a "metabolic transistor" approach was established. In this approach a small change in the level or availability of an essential component for the process is controlled by adding a competitive reaction that affects a precursor or an intermediate in its biosynthetic pathway. The change of the basal level of the essential component, considered as a base current in a transistor, has a large effect on the flux through the major pathway. In this way, the fine-tuning of a large flux can be accomplished. The "metabolic transistor" strategy was applied to control electron transfer chain function by manipulation of the quinone synthesis pathway in Escherichia coli. The achievement of a theoretical yield of lactate production under aerobic conditions via this strategy upon manipulation of the biosynthetic pathway of the key participant, ubiquinone-8 (Q8), in an E. coli strain provides an in vivo, genetically tunable means to control the activity of the electron transfer chain and manipulate the production of reduced products while limiting consumption of oxygen to a defined amount.

  3. In vivo enzyme activity in inborn errors of metabolism

    SciTech Connect

    Thompson, G.N.; Walter, J.H.; Leonard, J.V.; Halliday, D. )

    1990-08-01

    Low-dose continuous infusions of (2H5)phenylalanine, (1-13C)propionate, and (1-13C)leucine were used to quantitate phenylalanine hydroxylation in phenylketonuria (PKU, four subjects), propionate oxidation in methylmalonic acidaemia (MMA, four subjects), and propionic acidaemia (PA, four subjects) and leucine oxidation in maple syrup urine disease (MSUD, four subjects). In vivo enzyme activity in PKU, MMA, and PA subjects was similar to or in excess of that in adult controls (range of phenylalanine hydroxylation in PKU, 3.7 to 6.5 mumol/kg/h, control 3.2 to 7.9, n = 7; propionate oxidation in MMA, 15.2 to 64.8 mumol/kg/h, and in PA, 11.1 to 36.0, control 5.1 to 19.0, n = 5). By contrast, in vivo leucine oxidation was undetectable in three of the four MSUD subjects (less than 0.5 mumol/kg/h) and negligible in the remaining subject (2 mumol/kg/h, control 10.4 to 15.7, n = 6). These results suggest that significant substrate removal can be achieved in some inborn metabolic errors either through stimulation of residual enzyme activity in defective enzyme systems or by activation of alternate metabolic pathways. Both possibilities almost certainly depend on gross elevation of substrate concentrations. By contrast, only minimal in vivo oxidation of leucine appears possible in MSUD.

  4. [Ultrastructure and metabolic activity of pea mitochondria under clinorotation].

    PubMed

    Brykov, V A; Generozova, I P; Shugaev, A G

    2012-01-01

    Experimental data on the mitochondrial ultrastructure and tissue respiration in root apex as well as metabolic activity of the organelles isolated from pea seedling roots after 5-day of clinorotation are presented. It was shown that mitochondrial condensation in the distal elongation zone correlated with an increased rate of oxygen uptake on 7%. We also observed increase in rate of malate oxidation and respiratory control ratio increased simultaneously with a decreased in efficiency of oxidative phosphorylation. Such character of mitochondrial rearrangements in simulated microgravity is assumed to be a consequence of adaptation to these conditions.

  5. Phagocytic Activity Is Impaired in Type 2 Diabetes Mellitus and Increases after Metabolic Improvement

    PubMed Central

    Petriz, Jordi; Hernández, Cristina; Simó, Rafael

    2011-01-01

    Objective 1) To evaluate whether peripheral blood mononuclear cells (PBMCs) from type 2 diabetic patients present an impairment of phagocytic activity; 2) To determine whether the eventual impairment in phagocytic activity is related to glycemic control and can be reversed by improving blood glucose levels. Methods 21 type 2 diabetic patients and 21 healthy volunteers were prospectively recruited for a case-control study. In addition, those patients in whom HbA1c was higher than 8% (n = 12) were hospitalized in order to complete a 5-day intensification treatment of blood glucose. Phagocytic activity was assessed by using a modified flow cytometry procedure developed in our laboratory based on DNA/RNA viable staining to discriminate erythrocytes and debris. This method is simple, highly sensitive and reproducible and it takes advantage of classic methods that are widely used in flow cytometry. Results Type 2 diabetic patients showed a lower percentage of activated macrophages in comparison with non-diabetic subjects (54.00±18.93 vs 68.53±12.77%; p = 0.006) Significant negative correlations between phagocytic activity and fasting glucose (r = −0.619, p = 0.004) and HbA1c (r = −0.506, p = 0.019) were detected. In addition, multiple linear regression analyses showed that either fasting plasma glucose or HbA1c were independently associated with phagocytic activity. Furthermore, in the subset of patients who underwent metabolic optimization a significant increase in phagocytic activity was observed (p = 0.029). Conclusions Glycemic control is related to phagocytic activity in type 2 diabetes. Our results suggest that improvement in phagocytic activity can be added to the beneficial effects of metabolic optimization. PMID:21876749

  6. Assays of physical stability and antioxidant activity of a topical formulation added with different plant extracts.

    PubMed

    Di Mambro, Valéria M; Fonseca, Maria J V

    2005-02-23

    In the present investigation the changes on physical stability (pH, viscosity, flow index and tixotropy) of topical formulations were evaluated following inclusion of different plant extracts containing flavonoids. Also, the antioxidant effect of these plant extracts alone and after addition in the formulation was evaluated using chemiluminescence and the stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH(.-)) assays, as well as the inhibition of lipid peroxidation. Formulation added with dl-alpha-tocopherol was used to compare the physical stability and antioxidant activity. Formulations with plant extracts showed pseudoplastic behavior with decreasing on viscosity and tixotropy. The Glycyrrhiza glabra (GG) and Ginkgo biloba (GB) extracts alone and the formulations containing these extracts showed great antioxidant and free radical scavenging activities while the other extracts studied (mixture of Glycyrrhiza glabra, Symphytum officinale L and Arctium majus root, Nelumbium speciosum and soybean) showed lower activity. The results suggest that GG and GB extracts may be used in topical formulations in order to protect skin against damage caused by free radical and reactive oxygen species. PMID:15708669

  7. Muscle metabolic function and free-living physical activity.

    PubMed

    Hunter, Gary R; Larson-Meyer, D Enette; Sirikul, Bovorn; Newcomer, Bradley R

    2006-11-01

    We have previously shown that muscle metabolic function measured during exercise is related to exercise performance and subsequent 1-yr weight gain. Because it is well established that physical activity is important in weight maintenance, we examined muscle function relationships with free-living energy expenditure and physical activity. Subjects were 71 premenopausal black and white women. Muscle metabolism was evaluated by (31)P magnetic resonance spectroscopy during 90-s isometric plantar flexion contractions (45% maximum). Free-living energy expenditure (TEE) was measured using doubly labeled water, activity-related energy expenditure (AEE) was calculated as 0.9 x TEE - sleeping energy expenditure from room calorimetry, and free-living physical activity (ARTE) was calculated by dividing AEE by energy cost of standard physical activities. At the end of exercise, anaerobic glycolytic rate (ANGLY) and muscle concentration of phosphomonoesters (PME) were negatively related to TEE, AEE, and ARTE (P < 0.05). Multiple regression analysis showed that both PME (partial r = -0.29, <0.02) and ANGLY (partial r = -0.24, P < 0.04) were independently related to ARTE. PME, primarily glucose-6-phosphate and fructose-6-phosphate, was significantly related to ratings of perceived exertion (r = 0.21, P < or = 0.05) during a maximal treadmill test. PME was not related to ARTE after inclusion of RPE in the multiple regression model, suggesting that PME may be obtaining its relationship with ARTE through an increased perception of effort during physical activity. In conclusion, physically inactive individuals tend to be more dependent on anaerobic glycolysis during exercise while relying on a glycolytic pathway that may not be functioning optimally. PMID:16825516

  8. Muscle metabolic function and free-living physical activity.

    PubMed

    Hunter, Gary R; Larson-Meyer, D Enette; Sirikul, Bovorn; Newcomer, Bradley R

    2006-11-01

    We have previously shown that muscle metabolic function measured during exercise is related to exercise performance and subsequent 1-yr weight gain. Because it is well established that physical activity is important in weight maintenance, we examined muscle function relationships with free-living energy expenditure and physical activity. Subjects were 71 premenopausal black and white women. Muscle metabolism was evaluated by (31)P magnetic resonance spectroscopy during 90-s isometric plantar flexion contractions (45% maximum). Free-living energy expenditure (TEE) was measured using doubly labeled water, activity-related energy expenditure (AEE) was calculated as 0.9 x TEE - sleeping energy expenditure from room calorimetry, and free-living physical activity (ARTE) was calculated by dividing AEE by energy cost of standard physical activities. At the end of exercise, anaerobic glycolytic rate (ANGLY) and muscle concentration of phosphomonoesters (PME) were negatively related to TEE, AEE, and ARTE (P < 0.05). Multiple regression analysis showed that both PME (partial r = -0.29, <0.02) and ANGLY (partial r = -0.24, P < 0.04) were independently related to ARTE. PME, primarily glucose-6-phosphate and fructose-6-phosphate, was significantly related to ratings of perceived exertion (r = 0.21, P < or = 0.05) during a maximal treadmill test. PME was not related to ARTE after inclusion of RPE in the multiple regression model, suggesting that PME may be obtaining its relationship with ARTE through an increased perception of effort during physical activity. In conclusion, physically inactive individuals tend to be more dependent on anaerobic glycolysis during exercise while relying on a glycolytic pathway that may not be functioning optimally.

  9. Activation of AMP-Activated Protein Kinase and Stimulation of Energy Metabolism by Acetic Acid in L6 Myotube Cells.

    PubMed

    Maruta, Hitomi; Yoshimura, Yukihiro; Araki, Aya; Kimoto, Masumi; Takahashi, Yoshitaka; Yamashita, Hiromi

    2016-01-01

    Previously, we found that orally administered acetic acid decreased lipogenesis in the liver and suppressed lipid accumulation in adipose tissue of Otsuka Long-Evans Tokushima Fatty rats, which exhibit hyperglycemic obesity with hyperinsulinemia and insulin resistance. Administered acetic acid led to increased phosphorylation of AMP-activated protein kinase (AMPK) in both liver and skeletal muscle cells, and increased transcripts of myoglobin and glucose transporter 4 (GLUT4) genes in skeletal muscle of the rats. It was suggested that acetic acid improved the lipid metabolism in skeletal muscles. In this study, we examined the activation of AMPK and the stimulation of GLUT4 and myoglobin expression by acetic acid in skeletal muscle cells to clarify the physiological function of acetic acid in skeletal muscle cells. Acetic acid added to culture medium was taken up rapidly by L6 cells, and AMPK was phosphorylated upon treatment with acetic acid. We observed increased gene and protein expression of GLUT4 and myoglobin. Uptake of glucose and fatty acids by L6 cells were increased, while triglyceride accumulation was lower in treated cells compared to untreated cells. Furthermore, treated cells also showed increased gene and protein expression of myocyte enhancer factor 2A (MEF2A), which is a well-known transcription factor involved in the expression of myoglobin and GLUT4 genes. These results indicate that acetic acid enhances glucose uptake and fatty acid metabolism through the activation of AMPK, and increases expression of GLUT4 and myoglobin.

  10. Activation of AMP-Activated Protein Kinase and Stimulation of Energy Metabolism by Acetic Acid in L6 Myotube Cells.

    PubMed

    Maruta, Hitomi; Yoshimura, Yukihiro; Araki, Aya; Kimoto, Masumi; Takahashi, Yoshitaka; Yamashita, Hiromi

    2016-01-01

    Previously, we found that orally administered acetic acid decreased lipogenesis in the liver and suppressed lipid accumulation in adipose tissue of Otsuka Long-Evans Tokushima Fatty rats, which exhibit hyperglycemic obesity with hyperinsulinemia and insulin resistance. Administered acetic acid led to increased phosphorylation of AMP-activated protein kinase (AMPK) in both liver and skeletal muscle cells, and increased transcripts of myoglobin and glucose transporter 4 (GLUT4) genes in skeletal muscle of the rats. It was suggested that acetic acid improved the lipid metabolism in skeletal muscles. In this study, we examined the activation of AMPK and the stimulation of GLUT4 and myoglobin expression by acetic acid in skeletal muscle cells to clarify the physiological function of acetic acid in skeletal muscle cells. Acetic acid added to culture medium was taken up rapidly by L6 cells, and AMPK was phosphorylated upon treatment with acetic acid. We observed increased gene and protein expression of GLUT4 and myoglobin. Uptake of glucose and fatty acids by L6 cells were increased, while triglyceride accumulation was lower in treated cells compared to untreated cells. Furthermore, treated cells also showed increased gene and protein expression of myocyte enhancer factor 2A (MEF2A), which is a well-known transcription factor involved in the expression of myoglobin and GLUT4 genes. These results indicate that acetic acid enhances glucose uptake and fatty acid metabolism through the activation of AMPK, and increases expression of GLUT4 and myoglobin. PMID:27348124

  11. Activation of AMP-Activated Protein Kinase and Stimulation of Energy Metabolism by Acetic Acid in L6 Myotube Cells

    PubMed Central

    Maruta, Hitomi; Yoshimura, Yukihiro; Araki, Aya; Kimoto, Masumi; Takahashi, Yoshitaka; Yamashita, Hiromi

    2016-01-01

    Previously, we found that orally administered acetic acid decreased lipogenesis in the liver and suppressed lipid accumulation in adipose tissue of Otsuka Long-Evans Tokushima Fatty rats, which exhibit hyperglycemic obesity with hyperinsulinemia and insulin resistance. Administered acetic acid led to increased phosphorylation of AMP-activated protein kinase (AMPK) in both liver and skeletal muscle cells, and increased transcripts of myoglobin and glucose transporter 4 (GLUT4) genes in skeletal muscle of the rats. It was suggested that acetic acid improved the lipid metabolism in skeletal muscles. In this study, we examined the activation of AMPK and the stimulation of GLUT4 and myoglobin expression by acetic acid in skeletal muscle cells to clarify the physiological function of acetic acid in skeletal muscle cells. Acetic acid added to culture medium was taken up rapidly by L6 cells, and AMPK was phosphorylated upon treatment with acetic acid. We observed increased gene and protein expression of GLUT4 and myoglobin. Uptake of glucose and fatty acids by L6 cells were increased, while triglyceride accumulation was lower in treated cells compared to untreated cells. Furthermore, treated cells also showed increased gene and protein expression of myocyte enhancer factor 2A (MEF2A), which is a well-known transcription factor involved in the expression of myoglobin and GLUT4 genes. These results indicate that acetic acid enhances glucose uptake and fatty acid metabolism through the activation of AMPK, and increases expression of GLUT4 and myoglobin. PMID:27348124

  12. Effects of feeding wheat straw or orchardgrass at ad libitum or restricted intake during the dry period on postpartum performance and lipid metabolism.

    PubMed

    Litherland, N B; Weich, W D; Hansen, W P; Linn, J G

    2012-12-01

    The objectives of this study were to investigate the effects of forage source [wheat straw (WS) or orchardgrass hay (OG)] and total amount of diet dry matter fed [ad libitum or restricted to 70% of predicted dry matter intake (DMI)] prepartum on postpartum performance. The study design was a 2×2 factorial design with 10 cows per treatment. Treatments were WS total mixed ration (TMR) ad libitum, OG TMR ad libitum, WS TMR restricted, and OG TMR restricted. The WS TMR (dry matter basis) contained 30% WS, 20.7% corn silage, 10.0% alfalfa hay, 18.2% ground corn, 16.8% soybean meal, and 4.3% molasses mineral mix (14.7% CP, 1.5 Mcal/kg of net energy for lactation, 37.0% neutral detergent fiber). The OG TMR contained 30% OG, 46.2% corn silage, 10.0% alfalfa hay, 9.5% soybean meal, and 4.3% molasses (14.2% CP, 1.5 Mcal/kg of net energy for lactation, 41.0% neutral detergent fiber). Cows received 1 lactation diet after calving (17.7% CP, 1.6 Mcal/kg of net energy for lactation, 27.3% neutral detergent fiber). Total diet DMI prepartum was higher for ad libitum than for restricted as designed, but forage source had no effect on DMI. Total tract apparent digestibilities of DM and NDF were greater for OG than for WS. Postpartum DMI expressed as a percentage of body weight for the first week of lactation was higher for ad libitum than for restricted diets. Postpartum DMI during the first 30 d of lactation was higher for OG than for WS, but no effect was observed for the amount fed prepartum. Milk yield during the first week of lactation was higher for OG than for WS; however, during the first 30 d, 3.5% fat-corrected milk yield and yield of milk fat were highest for OG TMR restricted and WS TMR ad libitum. Prepartum treatments had a limited effect on pre- and postpartum lipid metabolism; however, cows fed WS TMR ad libitum had the highest postpartum β-hydroxybutyrate. Eating behavior was observed by 10-min video scans of 24-h video surveillance for 5d pre- and postpartum

  13. Spatial learning-related changes in metabolic activity of limbic structures at different posttask delays.

    PubMed

    Méndez-López, M; Méndez, M; Sampedro-Piquero, P; Arias, J L

    2013-01-01

    The aim of this study was to assess the functional contribution of brain limbic system regions at different moments after the acquisition of a short-term spatial memory task performed in the Morris water maze. Adult male Wistar rats were submitted to a matching-to-sample procedure with a hidden platform. The trials were made up of two daily identical visits to the platform, sample (swim-1) and retention (swim-2). To study oxidative metabolic activity, we applied cytochrome oxidase (COx) histochemistry. Densitometric measurements were taken at 1.5, 6, 24, and 48 hr posttask. An untrained group was added to explore the COx changes not specific to the learning process. The brain regions studied showed a different pattern of metabolic activity at different time points after the spatial memory task. Specifically, a significant increase of COx was found in the septal dentate gyrus, anteromedial thalamus, medial mammillary nucleus, and entorhinal cortex at early moments after learning. The entorhinal cortex maintained an increase of COx at later stages of the posttask period. In addition, an increase of COx activity was found in the supramammillary nucleus and the retrosplenial, perirhinal, and parietal cortices a long time after learning. These findings suggest that diencephalic and cortical regions are involved in this spatial learning and contribute at different moments to process this information.

  14. Metabolic Equivalent in Adolescents, Active Adults and Pregnant Women.

    PubMed

    Melzer, Katarina; Heydenreich, Juliane; Schutz, Yves; Renaud, Anne; Kayser, Bengt; Mäder, Urs

    2016-01-01

    "Metabolic Equivalent" (MET) represents a standard amount of oxygen consumed by the body under resting conditions, and is defined as 3.5 mL O₂/kg × min or ~1 kcal/kg × h. It is used to express the energy cost of physical activity in multiples of MET. However, universal application of the 1-MET standard was questioned in previous studies, because it does not apply well to all individuals. Height, weight and resting metabolic rate (RMR, measured by indirect calorimetry) were measured in adolescent males (n = 50) and females (n = 50), women during pregnancy (gestation week 35-41, n = 46), women 24-53 weeks postpartum (n = 27), and active men (n = 30), and were compared to values predicted by the 1-MET standard. The RMR of adolescent males (1.28 kcal/kg × h) was significantly higher than that of adolescent females (1.11 kcal/kg × h), with or without the effects of puberty stage and physical activity levels. The RMR of the pregnant and post-pregnant subjects were not significantly different. The RMR of the active normal weight (0.92 kcal/kg × h) and overweight (0.89 kcal/kg × h) adult males were significantly lower than the 1-MET value. It follows that the 1-MET standard is inadequate for use not only in adult men and women, but also in adolescents and physically active men. It is therefore recommended that practitioners estimate RMR with equations taking into account individual characteristics, such as sex, age and Body Mass Index, and not rely on the 1-MET standard. PMID:27447667

  15. Metabolic Equivalent in Adolescents, Active Adults and Pregnant Women

    PubMed Central

    Melzer, Katarina; Heydenreich, Juliane; Schutz, Yves; Renaud, Anne; Kayser, Bengt; Mäder, Urs

    2016-01-01

    Metabolic Equivalent” (MET) represents a standard amount of oxygen consumed by the body under resting conditions, and is defined as 3.5 mL O2/kg × min or ~1 kcal/kg × h. It is used to express the energy cost of physical activity in multiples of MET. However, universal application of the 1-MET standard was questioned in previous studies, because it does not apply well to all individuals. Height, weight and resting metabolic rate (RMR, measured by indirect calorimetry) were measured in adolescent males (n = 50) and females (n = 50), women during pregnancy (gestation week 35–41, n = 46), women 24–53 weeks postpartum (n = 27), and active men (n = 30), and were compared to values predicted by the 1-MET standard. The RMR of adolescent males (1.28 kcal/kg × h) was significantly higher than that of adolescent females (1.11 kcal/kg × h), with or without the effects of puberty stage and physical activity levels. The RMR of the pregnant and post-pregnant subjects were not significantly different. The RMR of the active normal weight (0.92 kcal/kg × h) and overweight (0.89 kcal/kg × h) adult males were significantly lower than the 1-MET value. It follows that the 1-MET standard is inadequate for use not only in adult men and women, but also in adolescents and physically active men. It is therefore recommended that practitioners estimate RMR with equations taking into account individual characteristics, such as sex, age and Body Mass Index, and not rely on the 1-MET standard. PMID:27447667

  16. Antifungal activity by vapor contact of essential oils added to amaranth, chitosan, or starch edible films.

    PubMed

    Avila-Sosa, Raúl; Palou, Enrique; Jiménez Munguía, María Teresa; Nevárez-Moorillón, Guadalupe Virginia; Navarro Cruz, Addí Rhode; López-Malo, Aurelio

    2012-02-01

    Antimicrobial agents can be incorporated into edible films to provide microbiological stability, since films can be used as carriers of a variety of additives to extend product shelf life and reduce the risk of microbial growth on food surfaces. Addition of antimicrobial agents to edible films offers advantages such as the use of small antimicrobial concentrations and low diffusion rates. The aim of this study was to evaluate inhibition by vapor contact of Aspergillus niger and Penicillium digitatum by selected concentrations of Mexican oregano (Lippia berlandieri Schauer), cinnamon (Cinnamomum verum) or lemongrass (Cymbopogon citratus) essential oils (EOs) added to amaranth, chitosan, or starch edible films. Essential oils were characterized by gas chromatography-mass spectrometry (GC/MS) analysis. Amaranth, chitosan and starch edible films were formulated with essential oil concentrations of 0.00, 0.25, 0.50, 0.75, 1.00, 2.00, or 4.00%. Antifungal activity was evaluated by determining the mold radial growth on agar media inoculated with A. niger and P. digitatum after exposure to vapors arising from essential oils added to amaranth, chitosan or starch films using the inverted lid technique. The modified Gompertz model adequately described mold growth curves (mean coefficient of determination 0.991 ± 0.05). Chitosan films exhibited better antifungal effectiveness (inhibition of A. niger with 0.25% of Mexican oregano and cinnamon EO; inhibition of P. digitatum with 0.50% EOs) than amaranth films (2.00 and 4.00% of cinnamon and Mexican oregano EO were needed to inhibit the studied molds, respectively). For chitosan and amaranth films a significant increase (p<0.05) of lag phase was observed among film concentrations while a significant decrease (p<0.05) of maximum specific growth was determined. Chitosan edible films incorporating Mexican oregano or cinnamon essential oil could improve the quality of foods by the action of the volatile compounds on surface growth

  17. Antifungal activity by vapor contact of essential oils added to amaranth, chitosan, or starch edible films.

    PubMed

    Avila-Sosa, Raúl; Palou, Enrique; Jiménez Munguía, María Teresa; Nevárez-Moorillón, Guadalupe Virginia; Navarro Cruz, Addí Rhode; López-Malo, Aurelio

    2012-02-01

    Antimicrobial agents can be incorporated into edible films to provide microbiological stability, since films can be used as carriers of a variety of additives to extend product shelf life and reduce the risk of microbial growth on food surfaces. Addition of antimicrobial agents to edible films offers advantages such as the use of small antimicrobial concentrations and low diffusion rates. The aim of this study was to evaluate inhibition by vapor contact of Aspergillus niger and Penicillium digitatum by selected concentrations of Mexican oregano (Lippia berlandieri Schauer), cinnamon (Cinnamomum verum) or lemongrass (Cymbopogon citratus) essential oils (EOs) added to amaranth, chitosan, or starch edible films. Essential oils were characterized by gas chromatography-mass spectrometry (GC/MS) analysis. Amaranth, chitosan and starch edible films were formulated with essential oil concentrations of 0.00, 0.25, 0.50, 0.75, 1.00, 2.00, or 4.00%. Antifungal activity was evaluated by determining the mold radial growth on agar media inoculated with A. niger and P. digitatum after exposure to vapors arising from essential oils added to amaranth, chitosan or starch films using the inverted lid technique. The modified Gompertz model adequately described mold growth curves (mean coefficient of determination 0.991 ± 0.05). Chitosan films exhibited better antifungal effectiveness (inhibition of A. niger with 0.25% of Mexican oregano and cinnamon EO; inhibition of P. digitatum with 0.50% EOs) than amaranth films (2.00 and 4.00% of cinnamon and Mexican oregano EO were needed to inhibit the studied molds, respectively). For chitosan and amaranth films a significant increase (p<0.05) of lag phase was observed among film concentrations while a significant decrease (p<0.05) of maximum specific growth was determined. Chitosan edible films incorporating Mexican oregano or cinnamon essential oil could improve the quality of foods by the action of the volatile compounds on surface growth

  18. Effect of sedentary activities on resting metabolic rate.

    PubMed

    Dietz, W H; Bandini, L G; Morelli, J A; Peers, K F; Ching, P L

    1994-03-01

    We examined the effect of television viewing on resting metabolic rate (RMR) in a cohort of 9 obese and 18 nonobese girls aged 10.4 +/- 1.1 y. RMR was measured while girls watched television, read, or sat quietly for 15 min. Movement was assessed by using activity monitors and a manual count of movements observed on a videotape. Absolute RMR was greater for the obese girls, but no significant treatment effect existed for absolute RMR within either group. Although measured activity did not differ, observed movements were greater when the girls were sitting quietly. Total observed and measured movements were significantly correlated with the CV of the minute-by-minute RMR. These results suggest that television viewing does not alter RMR. Although children appear to fidget more when sitting quietly than when they read or watch television, fidgeting appears to affect the minute-to-minute variation of RMR rather than the level of resting energy expenditure.

  19. Metabolic Pathways In Immune Cell Activation And Quiescence

    PubMed Central

    Pearce, Erika L.; Pearce, Edward J.

    2013-01-01

    Studies of immune system metabolism (“immunometabolism”) segregate along two paths. The first investigates the effects of immune cells on organs that regulate whole body metabolism, such as adipose tissue and liver. The second explores the role of metabolic pathways within immune cells and how this regulates immune response outcome. Distinct metabolic pathways diverge and converge at many levels and cells therefore face choices in how to achieve their metabolic goals. There is interest in fully understanding how and why immune cells commit to particular metabolic fates, and in elucidating the immunologic consequences of reaching a metabolic endpoint by one pathway versus another. This is particularly intriguing since metabolic commitment is influenced not only by substrate availability, but also by signaling pathways elicited by metabolites. Thus metabolic choices in cells enforce fate and function and this area will be the subject of this review. PMID:23601682

  20. Spatial memory extinction differentially affects dorsal and ventral hippocampal metabolic activity and associated functional brain networks.

    PubMed

    Méndez-Couz, Marta; González-Pardo, Héctor; Vallejo, Guillermo; Arias, Jorge L; Conejo, Nélida M

    2016-10-01

    Previous studies showed the involvement of brain regions associated with both spatial learning and associative learning in spatial memory extinction, although the specific role of the dorsal and ventral hippocampus and the extended hippocampal system including the mammillary body in the process is still controversial. The present study aimed to identify the involvement of the dorsal and ventral hippocampus, together with cortical regions, the amygdaloid nuclei, and the mammillary bodies in the extinction of a spatial memory task. To address these issues, quantitative cytochrome c oxidase histochemistry was applied as a metabolic brain mapping method. Rats were trained in a reference memory task using the Morris water maze, followed by an extinction procedure of the previously acquired memory task. Results show that rats learned successfully the spatial memory task as shown by the progressive decrease in measured latencies to reach the escape platform and the results obtained in the probe test. Spatial memory was subsequently extinguished as shown by the descending preference for the previously reinforced location. A control naïve group was added to ensure that brain metabolic changes were specifically related with performance in the spatial memory extinction task. Extinction of the original spatial learning task significantly modified the metabolic activity in the dorsal and ventral hippocampus, the amygdala and the mammillary bodies. Moreover, the ventral hippocampus, the lateral mammillary body and the retrosplenial cortex were differentially recruited in the spatial memory extinction task, as shown by group differences in brain metabolic networks. These findings provide new insights on the brain regions and functional brain networks underlying spatial memory, and specifically spatial memory extinction. © 2016 Wiley Periodicals, Inc.

  1. Spatial memory extinction differentially affects dorsal and ventral hippocampal metabolic activity and associated functional brain networks.

    PubMed

    Méndez-Couz, Marta; González-Pardo, Héctor; Vallejo, Guillermo; Arias, Jorge L; Conejo, Nélida M

    2016-10-01

    Previous studies showed the involvement of brain regions associated with both spatial learning and associative learning in spatial memory extinction, although the specific role of the dorsal and ventral hippocampus and the extended hippocampal system including the mammillary body in the process is still controversial. The present study aimed to identify the involvement of the dorsal and ventral hippocampus, together with cortical regions, the amygdaloid nuclei, and the mammillary bodies in the extinction of a spatial memory task. To address these issues, quantitative cytochrome c oxidase histochemistry was applied as a metabolic brain mapping method. Rats were trained in a reference memory task using the Morris water maze, followed by an extinction procedure of the previously acquired memory task. Results show that rats learned successfully the spatial memory task as shown by the progressive decrease in measured latencies to reach the escape platform and the results obtained in the probe test. Spatial memory was subsequently extinguished as shown by the descending preference for the previously reinforced location. A control naïve group was added to ensure that brain metabolic changes were specifically related with performance in the spatial memory extinction task. Extinction of the original spatial learning task significantly modified the metabolic activity in the dorsal and ventral hippocampus, the amygdala and the mammillary bodies. Moreover, the ventral hippocampus, the lateral mammillary body and the retrosplenial cortex were differentially recruited in the spatial memory extinction task, as shown by group differences in brain metabolic networks. These findings provide new insights on the brain regions and functional brain networks underlying spatial memory, and specifically spatial memory extinction. © 2016 Wiley Periodicals, Inc. PMID:27102086

  2. Solar activity and climate change during the 1750 A.D. solar minimum

    NASA Astrophysics Data System (ADS)

    Bard, Edouard; Baroni, Mélanie; Aster Team

    2015-04-01

    The number of sunspots and other characteristics have been widely used to reconstruct the solar activity beyond the last three decades of accurate satellite measurements. It has also been possible to reconstruct the long-term solar behavior by measuring the abundance on Earth of cosmogenic nuclides such as carbon 14 and beryllium 10. These isotopes are formed by the interaction of galactic cosmic rays with atmospheric molecules. Accelerator mass spectrometry is used to measure the abundance of these isotopes in natural archives such as polar ice (for 10Be), tree rings and corals (for 14C). Over the last millennium, the solar activity has been dominated by alternating active and quiet periods, such as the Maunder Minimum, which occurred between 1645 and 1715 A.D. The climate forcing of this solar variability is the subject of intense research, both because the exact scaling in terms of irradiance is still a matter of debate and because other solar variations may have played a role in amplifying the climatic response. Indeed, the past few decades of accurate solar measurements do not include conditions equivalent to an extended solar minimum. A further difficulty of the analysis lies in the presence of other climate forcings during the last millennium, which are superimposed on the solar variations. Finally, the inherent precision of paleotemperature proxies are close to the signal amplitude retrieved from various paleoclimate archives covering the last millennium. Recent model-data comparisons for the last millennium have led to the conclusion that the solar forcing during this period was minor in comparison to volcanic eruptions and greenhouse gas concentrations (e.g. Schurer et al. 2013 J. Clim., 2014 Nat. Geo.). In order to separate the different forcings, it is useful to focus on a temperature change in phase with a well-documented solar minimum so as to maximize the response to this astronomical forcing. This is the approach followed by Wagner et al. (2005 Clim

  3. Mutagenicity of 3-chlorodibenzofuran and its metabolic activation

    SciTech Connect

    Matsumoto, Michi; Ando, Mitsuru )

    1991-01-01

    3-Chlorodibenzofuran was the only markedly mutagenic isomer among the four monochlorodibenzofurans. Although it was mutagenic even in the absence of 9,000g supernatant fraction (S9) of rat liver, it was further activated by the addition of S9. Metabolic activation of this compound in mutagenicity was studied using liver S9s and cell fractions which were prepared from rats treated with two inducers. 1,1-Dichloro-2,2-bis(p-chlorophenyl) ethylene (DDE) was used as an inducer of phenobarbital inducible cytochrome P-450, and {beta}-naphthoflavone ({beta}NF) was used as an inducer of 3-methylcholanthrene inducible cytochrome P-448. Mutagenicity was tested using Salmonella typhimurium tester strain TA98, because this strain is more sensitive to 3-chlorodibenzofuran than strain TA100. This experiment showed that 3-chlorodibenzofuran was activated most highly by {beta}NF-induced microsomes. However, it was also activated by the cytosolic fraction. This showed that 3-chlorodibenzofuran is activated not only by cytochrome P-448, which is induced by 3-methylcholanthrene type inducers, but also by the enzymes existing in normal rat liver. This result suggests a risk of manifestation of its toxicity to normal animals.

  4. Metabolism

    MedlinePlus

    Metabolism refers to all the physical and chemical processes in the body that convert or use energy, ... Tortora GJ, Derrickson BH. Metabolism. In: Tortora GJ, Derrickson BH. Principles of Anatomy and Physiology . 14th ed. Hoboken, NJ: John H Wiley and Sons; 2013: ...

  5. Chromium uptake and toxicity effects on growth and metabolic activities in wheat, Triticum aestivum L. cv. UP 2003.

    PubMed

    Sharma, D C; Sharma, C P

    1996-07-01

    Chromium (Cr) at graded levels when added in sand culture of wheat (T. aestivum L. cv. UP2003) under glasshouse conditions resulted in reduction in biomass, chlorophyll and activities of catalase and peroxidase while enhanced acid phosphatase and ribonuclease activities. Elevated levels of Cr supply significantly reduced the concentration of inorganic phosphorus. With an increase in Cr supply the uptake of chromium also increased significantly in different plant parts especially in roots. Above metabolic lesions due to Cr in wheat provided evidence that the element in nutrient medium if present in excess may be inhibitory to plant growth and development.

  6. Nanosilver induces a non-culturable but metabolically active state in Pseudomonas aeruginosa

    PubMed Central

    Königs, Alexa M.; Flemming, Hans-Curt; Wingender, Jost

    2015-01-01

    The antimicrobial properties of silver nanoparticles (AgNPs) have raised expectations for the protection of medical devices and consumer products against biofilms. The effect of silver on bacteria is commonly determined by culture-dependent methods. It is as yet unknown if silver-exposed bacteria can enter a metabolically active but non-culturable state. In this study, the efficacy of chemically synthesized AgNPs and silver as silver nitrate (AgNO3) against planktonic cells and biofilms of Pseudomonas aeruginosa AdS was investigated in microtiter plate assays, using cultural as well as culture-independent methods. In liquid medium, AgNPs and AgNO3 inhibited both planktonic growth and biofilm formation. The efficacy of AgNPs and AgNO3 against established, 24 h-old biofilms and planktonic stationary-phase cells was compared by exposure to silver in deionized water. Loss of culturability of planktonic cells was always higher than that of the attached biofilms. However, resuspended biofilm cells became more susceptible to AgNPs and AgNO3 than attached biofilms. Thus, the physical state of bacteria within biofilms rendered them more tolerant to silver compared with the planktonic state. Silver-exposed cells that had become unculturable still displayed signs of viability: they contained rRNA, determined by fluorescent in situ hybridization, as an indicator for potential protein synthesis, maintained their membrane integrity as monitored by differential live/dead staining, and displayed significant levels of adenosine triphosphate. It was concluded that AgNPs and AgNO3 in concentrations at which culturability was inhibited, both planktonic and biofilm cells of P. aeruginosa were still intact and metabolically active, reminiscent of the viable but non-culturable state known to be induced in pathogenic bacteria in response to stress conditions. This observation is important for a realistic assessment of the antimicrobial properties of AgNPs. PMID:25999929

  7. Biological Activities of Tetrodotoxin-Producing Enterococcus faecium AD1 Isolated from Puffer Fishes

    PubMed Central

    Nguyen, Tu Hoang Khue; Nguyen, Huu Ngoc; Nghe, Dat Van; Nguyen, Kim Hoang

    2015-01-01

    Puffer fishes were collected from the central sea in Vietnam from spring to summer season. The eggs were incubated in MRS broth that was used to test the toxicity in mice and isolate the lactic acid bacteria community that could produce tetrodotoxin (TTX). Thin layer chromatography (TLC) and high performance lipid chromatography (HPLC) were used to detect and quantify TTX. As a result, Enterococcus faecium AD1 which was identified by biochemical test and 16S rRNA analysis could produce TTX 0.3 mg/mL when cultured in MRS broth. The bacterium was optimized for TTX production and gave 0.18 mg/mL, 0.07 mg/mL, and 0.15 mg/mL in media prepared from the meat-washing water of freshwater fishes (Pangasius bocourti, Oreochromis sp.) and sea fish (Auxis thazard), respectively, that are also hopeful to answer some poisoning cases related to eating fishes. Enterococcus faecium also showed the wide antimicrobial activities on yeast, Gram-negative and -positive bacteria. Extracted exopolysaccharide (EPS) that reacted with 2,2-diphenyl-1-picrylhydrazyl to give IC50 at 5 mg/mL equaled 11 mg/mL ascorbic acid which could show effects on Hela-6 and Hep G2 using sulforhodamine B test. Enterococcus faecium can be claimed as a promising source in tetrodotoxin and biological compounds. PMID:26380310

  8. Biological Activities of Tetrodotoxin-Producing Enterococcus faecium AD1 Isolated from Puffer Fishes.

    PubMed

    Nguyen, Tu Hoang Khue; Nguyen, Huu Ngoc; Nghe, Dat Van; Nguyen, Kim Hoang

    2015-01-01

    Puffer fishes were collected from the central sea in Vietnam from spring to summer season. The eggs were incubated in MRS broth that was used to test the toxicity in mice and isolate the lactic acid bacteria community that could produce tetrodotoxin (TTX). Thin layer chromatography (TLC) and high performance lipid chromatography (HPLC) were used to detect and quantify TTX. As a result, Enterococcus faecium AD1 which was identified by biochemical test and 16S rRNA analysis could produce TTX 0.3 mg/mL when cultured in MRS broth. The bacterium was optimized for TTX production and gave 0.18 mg/mL, 0.07 mg/mL, and 0.15 mg/mL in media prepared from the meat-washing water of freshwater fishes (Pangasius bocourti, Oreochromis sp.) and sea fish (Auxis thazard), respectively, that are also hopeful to answer some poisoning cases related to eating fishes. Enterococcus faecium also showed the wide antimicrobial activities on yeast, Gram-negative and -positive bacteria. Extracted exopolysaccharide (EPS) that reacted with 2,2-diphenyl-1-picrylhydrazyl to give IC50 at 5 mg/mL equaled 11 mg/mL ascorbic acid which could show effects on Hela-6 and Hep G2 using sulforhodamine B test. Enterococcus faecium can be claimed as a promising source in tetrodotoxin and biological compounds. PMID:26380310

  9. Inferring the metabolism of human orphan metabolites from their metabolic network context affirms human gluconokinase activity.

    PubMed

    Rolfsson, Óttar; Paglia, Giuseppe; Magnusdóttir, Manuela; Palsson, Bernhard Ø; Thiele, Ines

    2013-01-15

    Metabolic network reconstructions define metabolic information within a target organism and can therefore be used to address incomplete metabolic information. In the present study we used a computational approach to identify human metabolites whose metabolism is incomplete on the basis of their detection in humans but exclusion from the human metabolic network reconstruction RECON 1. Candidate solutions, composed of metabolic reactions capable of explaining the metabolism of these compounds, were then identified computationally from a global biochemical reaction database. Solutions were characterized with respect to how metabolites were incorporated into RECON 1 and their biological relevance. Through detailed case studies we show that biologically plausible non-intuitive hypotheses regarding the metabolism of these compounds can be proposed in a semi-automated manner, in an approach that is similar to de novo network reconstruction. We subsequently experimentally validated one of the proposed hypotheses and report that C9orf103, previously identified as a candidate tumour suppressor gene, encodes a functional human gluconokinase. The results of the present study demonstrate how semi-automatic gap filling can be used to refine and extend metabolic reconstructions, thereby increasing their biological scope. Furthermore, we illustrate how incomplete human metabolic knowledge can be coupled with gene annotation in order to prioritize and confirm gene functions.

  10. INCREASED ENDOCRINE ACTIVITY OF XENOBIOTIC CHEMICALS AS MEDIATED BY METABOLIC ACTIVATION

    EPA Science Inventory

    This research is part of an effort to develop in vitro assays and QSARs applicable to untested chemicals on EPA inventories through study of estrogen receptor (ER) binding and estrogen mediated gene expression in fish. The current effort investigates metabolic activation of chemi...

  11. JunB potentiates function of BRCA1 activation domain 1 (AD1) through a coiled-coil-mediated interaction

    PubMed Central

    Hu, Yan-Fen; Li, Rong

    2002-01-01

    BRCA1 is involved in the regulation of multiple nuclear events including transcription. AD1, one of the two trans-activation domains in BRCA1, stimulates transcription in a cell context-dependent manner. Here, it is shown that BRCA1 interacts with Jun proteins via a coiled-coil motif in AD1 and the basic leucine zipper (bZIP) region of the Jun proteins. The Jun-interacting domain in BRCA1 is critical for AD1-mediated transcriptional activation. In particular, the strength of AD1 in transcriptional activation is limited by the JunB level and ectopic expression of JunB potentiates the transcriptional activity of AD1. Furthermore, JunB mRNA expression is down-regulated in many ovarian tumor tissues examined. Thus, the coiled-coil-mediated cooperation between BRCA1 and JunB may facilitate the function of these proteins in tissue-specific transcriptional regulation and tumor suppression. PMID:12080089

  12. Metabolic activation of aromatic amines and azo dyes.

    PubMed

    Bartsch, H

    1981-01-01

    Aromatic amines, amides and nitro compounds are a class of chemicals that produce tumors in a wide variety of tissues in experimental animals, including liver, urinary bladder, forestomach, small intestine, Zymbal's gland, subcutaneous tissue or skin. In man, exposure to some aromatic amines is associated with tumours of the urinary bladder and carcinoma of the renal pelvis. Their biological activity as carcinogens or genotoxic agents is, in all the cases that have been studied in detail, dependent on metabolic activation in vivo, occurring by multiple pathways. Differences in these metabolic pathways may largely account for the differences in tissues and species susceptibilities to cancer induction. Carcinogenicity of aromatic amines or amides is dependent on their oxidation to N-hydroxy derivatives, whilst the carcinogenicity of aromatic nitro compounds is linked to their reduction to hydroxylamines. Further conversion of the N-hydroxylamine or N-hydroxyamide to reactive intermediates can occur in several ways, which include (i) esterification of the N-hydroxy group, (ii) non-enzymic protonation of the nitrogen of the hydroxylamine and (iii) oxidation to a free radical of arylhydroxamic acids. Following generation of such reactive electrophilic intermediates in tissues or cells, macromolecular binding has been observed to nucleic acids and proteins. In many cases, arylamidated and arylaminated products are formed with nucleic acid bases; in the case of the well-studied 2-acetylaminofluorene, nucleophilic atoms of guanine are the predominant site of reaction. Relatively little is known of the structure and biological consequences of DNA adducts formed from other aromatic amines, amides or nitro compounds; more research in these directions is warranted.

  13. Metaproteomic analysis reveals microbial metabolic activities in the deep ocean

    NASA Astrophysics Data System (ADS)

    Wang, Da-Zhi; Xie, Zhang-Xian; Zhang, Shu-Feng; Wang, Ming-Hua; Zhang, Hao; Kong, Ling-Fen; Lin, Lin

    2016-04-01

    The deep sea is the largest habitat on earth and holds many and varied microbial life forms. However, little is known about their metabolic activities in the deep ocean. Here, we characterized protein profiles of particulate (>0.22 μm) and dissolved (between 10 kDa and 0.22 μm) fractions collected from the deep South China Sea using a shotgun proteomic approach. SAR324, Alteromonadales and SAR11 were the most abundant groups, while Prasinophyte contributed most to eukaryotes and cyanophage to viruses. The dominant heterotrophic activity was evidenced by the abundant transporters (33%). Proteins participating in nitrification, methanogenesis, methyltrophy and CO2 fixation were detected. Notably, the predominance of unique cellular proteins in dissolved fraction suggested the presence of membrane structures. Moreover, the detection of translation proteins related to phytoplankton indicated that other process rather than sinking particles might be the downward export of living cells. Our study implied that novel extracellular activities and the interaction of deep water with its overlying water could be crucial to the microbial world of deep sea.

  14. Phenomenological correlates of metabolic activity in 18 patients with chronic schizophrenia

    SciTech Connect

    Volkow, N.D.; Wolf, A.P.; Van Gelder, P.; Brodie, J.D.; Overall, J.E.; Cancro, R.; Gomez-Mont, F.

    1987-02-01

    Using (11C)-deoxy-D-glucose and positron emission tomography (PET), the authors measured brain metabolism in 18 patients with chronic schizophrenia to assess which of the metabolic measures from two test conditions was more closely related to the patients' differing clinical characteristics. The two conditions were resting and activation, and an eye tracking task was used. Patients with more negative symptoms showed lower global metabolic rates and more severe hypofrontality than did the patients with fewer negative symptoms. Differences among the patients were distinguished by the task: sicker patients failed to show a metabolic activation response. These findings suggest that cerebral metabolic patterns reflect clinical characteristics of schizophrenic patients.

  15. The metabolic activator FOXO1 binds hepatitis B virus DNA and activates its transcription

    SciTech Connect

    Shlomai, Amir; Shaul, Yosef

    2009-04-17

    Hepatitis B virus (HBV) is a small DNA virus that targets the liver and infects humans worldwide. Recently we have shown that the metabolic regulator PGC-1{alpha} coactivates HBV transcription thereby rendering the virus susceptible to fluctuations in the nutritional status of the liver. PGC-1{alpha} coactivation of HBV is mediated through the liver-enriched nuclear receptor HNF4{alpha} and through another yet unknown transcription factor(s). Here we show that the forkhead transcription factor FOXO1, a known target for PGC-1{alpha} coactivation and a central mediator of glucose metabolism in the liver, binds HBV core promoter and activates its transcription. This activation is further enhanced in the presence of PGC-1{alpha}, implying that FOXO1 is a target for PGC-1{alpha} coactivation of HBV transcription. Thus, our results identify another key metabolic regulator as an activator of HBV transcription, thereby supporting the principle that HBV gene expression is regulated in a similar way to key hepatic metabolic genes.

  16. Bioirrigation impacts on sediment respiration and microbial metabolic activity

    NASA Astrophysics Data System (ADS)

    Baranov, V. A.; Lewandowski, J.; Romeijn, P.; Krause, S.

    2015-12-01

    Some bioturbators build tubes in the sediment and pump water through their burrows (ventilation). Oxygen is transferred through the burrow walls in the adjacent sediment (bioirrigation). Bioirrigation is playing a pivotal role in the mediation of biogeochemical processes in lake sediments and has the potential to enhance nutrient cycling. The present study investigates the impact of bioirrigation on lake sediment metabolism, respiration rates and in particular, the biogeochemical impacts of bioirrigation intensity as a function of organism density. We therefore apply the bioreactive Resazurin/Resorufin smart tracer system for quantifying the impact of different densities of Chironomidae (Diptera) larvae (0-2112 larvae/m2) on lake sediment respiration in a microcosm experiment. Tracer decay has been found to be proportional to the amount of the aerobic respiration at the sediment-water interface. Tracer transformation was in good agreement with Chironomidae density (correlation, r=0.9). Tracer transformation rates (and sediment respiration) were found to be correlated to Chironomidae density, with highest transformation rates observed in the microcosms with highest density of 2112 larvae/m2. This relationship was not linear though, with sediment respiration rates at the highest larvae densities declining from the linear trend predicted from lower and intermediate larvae density-respiration relationships. We interpret this effect as a density dependent suppression of the Chironomid's metabolic activity. The observations of this study have implications for eutrophied lakes with high densities of bioirrigators. Despite high density of bioirrigirrigating benthos, mineralization of the organic matter in such habitats would likely be lower than in lakes with intermediate densities of the bioturbators.

  17. Metabolic signals and innate immune activation in obesity and exercise.

    PubMed

    Ringseis, Robert; Eder, Klaus; Mooren, Frank C; Krüger, Karsten

    2015-01-01

    The combination of a sedentary lifestyle and excess energy intake has led to an increased prevalence of obesity which constitutes a major risk factor for several co-morbidities including type 2 diabetes and cardiovascular diseases. Intensive research during the last two decades has revealed that a characteristic feature of obesity linking it to insulin resistance is the presence of chronic low-grade inflammation being indicative of activation of the innate immune system. Recent evidence suggests that activation of the innate immune system in the course of obesity is mediated by metabolic signals, such as free fatty acids (FFAs), being elevated in many obese subjects, through activation of pattern recognition receptors thereby leading to stimulation of critical inflammatory signaling cascades, like IκBα kinase/nuclear factor-κB (IKK/NF- κB), endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) and NOD-like receptor P3 (NLRP3) inflammasome pathway, that interfere with insulin signaling. Exercise is one of the main prescribed interventions in obesity management improving insulin sensitivity and reducing obesity- induced chronic inflammation. This review summarizes current knowledge of the cellular recognition mechanisms for FFAs, the inflammatory signaling pathways triggered by excess FFAs in obesity and the counteractive effects of both acute and chronic exercise on obesity-induced activation of inflammatory signaling pathways. A deeper understanding of the effects of exercise on inflammatory signaling pathways in obesity is useful to optimize preventive and therapeutic strategies to combat the increasing incidence of obesity and its comorbidities. PMID:25825956

  18. Metabolic activity of permafrost bacteria below the freezing point

    NASA Technical Reports Server (NTRS)

    Rivkina, E. M.; Friedmann, E. I.; McKay, C. P.; Gilichinsky, D. A.

    2000-01-01

    Metabolic activity was measured in the laboratory at temperatures between 5 and -20 degrees C on the basis of incorporation of (14)C-labeled acetate into lipids by samples of a natural population of bacteria from Siberian permafrost (permanently frozen soil). Incorporation followed a sigmoidal pattern similar to growth curves. At all temperatures, the log phase was followed, within 200 to 350 days, by a stationary phase, which was monitored until the 550th day of activity. The minimum doubling times ranged from 1 day (5 degrees C) to 20 days (-10 degrees C) to ca. 160 days (-20 degrees C). The curves reached the stationary phase at different levels, depending on the incubation temperature. We suggest that the stationary phase, which is generally considered to be reached when the availability of nutrients becomes limiting, was brought on under our conditions by the formation of diffusion barriers in the thin layers of unfrozen water known to be present in permafrost soils, the thickness of which depends on temperature.

  19. Metabolic Activity of Permafrost Bacteria below the Freezing Point

    PubMed Central

    Rivkina, E. M.; Friedmann, E. I.; McKay, C. P.; Gilichinsky, D. A.

    2000-01-01

    Metabolic activity was measured in the laboratory at temperatures between 5 and −20°C on the basis of incorporation of 14C-labeled acetate into lipids by samples of a natural population of bacteria from Siberian permafrost (permanently frozen soil). Incorporation followed a sigmoidal pattern similar to growth curves. At all temperatures, the log phase was followed, within 200 to 350 days, by a stationary phase, which was monitored until the 550th day of activity. The minimum doubling times ranged from 1 day (5°C) to 20 days (−10°C) to ca. 160 days (−20°C). The curves reached the stationary phase at different levels, depending on the incubation temperature. We suggest that the stationary phase, which is generally considered to be reached when the availability of nutrients becomes limiting, was brought on under our conditions by the formation of diffusion barriers in the thin layers of unfrozen water known to be present in permafrost soils, the thickness of which depends on temperature. PMID:10919774

  20. Metabolic and Cardiovascular Responses of Children during Prolonged Physical Activity.

    ERIC Educational Resources Information Center

    Chausow, Sharon A.; And Others

    1984-01-01

    Metabolic and cardiovascular responses during 45 minutes of continuous moderate intensity exercise were investigated in 11 children, 8-11 years of age. Results indicate that children exhibit metabolic and cardiovascular adjustments similar to those noted in adults during prolonged exercise. (Author/JMK)

  1. Transcriptional integration of metabolism by the nuclear sterol-activated receptors LXR and FXR

    PubMed Central

    2013-01-01

    Nuclear receptors are integrators of hormonal and nutritional signals, mediating changes to metabolic pathways within the body. Given that modulation of lipid and glucose metabolism has been linked to diseases including type 2 diabetes, obesity and atherosclerosis, a greater understanding of pathways that regulate metabolism in physiology and disease is crucial. The liver X receptors (LXRs) and the farnesoid X receptors (FXRs) are activated by oxysterols and bile acids, respectively. Mounting evidence indicates that these nuclear receptors have essential roles, not only in the regulation of cholesterol and bile acid metabolism but also in the integration of sterol, fatty acid and glucose metabolism. PMID:22414897

  2. Transcriptional integration of metabolism by the nuclear sterol-activated receptors LXR and FXR.

    PubMed

    Calkin, Anna C; Tontonoz, Peter

    2012-03-14

    Nuclear receptors are integrators of hormonal and nutritional signals, mediating changes to metabolic pathways within the body. Given that modulation of lipid and glucose metabolism has been linked to diseases including type 2 diabetes, obesity and atherosclerosis, a greater understanding of pathways that regulate metabolism in physiology and disease is crucial. The liver X receptors (LXRs) and the farnesoid X receptors (FXRs) are activated by oxysterols and bile acids, respectively. Mounting evidence indicates that these nuclear receptors have essential roles, not only in the regulation of cholesterol and bile acid metabolism but also in the integration of sterol, fatty acid and glucose metabolism.

  3. Model-driven multi-omic data analysis elucidates metabolic immunomodulators of macrophage activation

    SciTech Connect

    Bordbar, Aarash; Mo, Monica L.; Nakayasu, Ernesto S.; Rutledge, Alexandra C.; Kim, Young-Mo; Metz, Thomas O.; Jones, Marcus B.; Frank, Bryan C.; Smith, Richard D.; Peterson, Scott N.; Hyduke, Daniel R.; Adkins, Joshua N.; Palsson, Bernhard O.

    2012-06-26

    Macrophages are central players in the immune response, manifesting divergent phenotypes to control inflammation and innate immunity through the release of cytokines and other regulatory factor-dependent signaling pathways. In recent years, the focus on metabolism has been reemphasized as critical signaling and regulatory pathways of human pathophysiology, ranging from cancer to aging, often converge on metabolic responses. Here, we used genome-scale modeling and multi-omics (transcriptomics, proteomics, and metabolomics) analysis to assess metabolic features critical for macrophage functions. We constructed a genome-scale metabolic network for the RAW 264.7 cell line to determine metabolic modulators of macrophage activation. Metabolites well-known to be associated with immunoactivation (e.g., glucose and arginine) and immunosuppression (e.g., tryptophan and vitamin D3) were amongst the most critical effectors. Intracellular metabolic mechanisms linked to critical suppressive effectors were then assessed, identifying a suppressive role for de novo nucleotide synthesis. Finally, the underlying metabolic mechanisms of macrophage activation are identified by analyzing multi-omic data obtained from LPS-stimulated RAW cells in the context of our flux-based predictions. Our study demonstrates metabolism's role in regulating activation may be greater than previously anticipated and elucidates underlying metabolic connections between activation and metabolic effectors.

  4. Activation of AMP-kinase by Policosanol Requires Peroxisomal Metabolism

    PubMed Central

    Banerjee, Subhashis; Ghoshal, Sarbani

    2011-01-01

    Policosanol, a well-defined mixture of very long chain primary alcohols that is available as a nutraceutical product, has been reported to lower blood cholesterol levels. The present studies demonstrate that policosanol promotes the phosphorylation of AMP-kinase and HMG-CoA reductase in hepatoma cells and in mouse liver after intragastric administration, providing a possible means by which policosanol might lower blood cholesterol levels. Treatment of hepatoma cells with policosanol produced a 2.5-fold or greater increase in the phosphorylation of AMP-kinase and HMG-CoA reductase, and increased the phosphorylation of Ca++/calmodulin-dependent kinase kinase (CaMKK), an upstream AMP-kinase kinase. Intra-gastric administration of policosanol to mice similarly increased the phosphorylation of hepatic HMG-CoA reductase and AMP-kinase by greater than 2-fold. siRNA-mediated suppression of fatty aldehyde dehydrogenase, fatty acyl-CoA synthetase 4, and acyl-CoA acetyltransferase expression in hepatoma cells prevented the phosphorylation of AMP-kinase and HMG-CoA reductase by policosanol, indicating that metabolism of these very long chain alcohols to activated fatty acids is necessary for the suppression of cholesterol synthesis, presumably by increasing cellular AMP levels. Subsequent peroxisomal β-oxidation probably augments this effect. PMID:21359855

  5. Influence of host seed on metabolic activity by Enterobacter cloacae in the spermosphere

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Little is known regarding the influences of nutrients released from plants on the metabolic activity of colonizing microbes. To gain a better understanding of these influences, we used bioluminescence- and oxygen consumption-based methods to compare bacterial metabolic activity expressed during col...

  6. Acclimation of aerobic-activated sludge degrading benzene derivatives and co-metabolic degradation activities of trichloroethylene by benzene derivative-grown aerobic sludge.

    PubMed

    Wang, Shizong; Yang, Qi; Bai, Zhiyong; Wang, Shidong; Wang, Yeyao; Nowak, Karolina M

    2015-01-01

    The acclimation of aerobic-activated sludge for degradation of benzene derivatives was investigated in batch experiments. Phenol, benzoic acid, toluene, aniline and chlorobenzene were concurrently added to five different bioreactors which contained the aerobic-activated sludge. After the acclimation process ended, the acclimated phenol-, benzoic acid-, toluene-, aniline- and chlorobenzene-grown aerobic-activated sludge were used to explore the co-metabolic degradation activities of trichloroethylene (TCE). Monod equation was employed to simulate the kinetics of co-metabolic degradation of TCE by benzene derivative-grown sludge. At the end of experiments, the mixed microbial communities grown under different conditions were identified. The results showed that the acclimation periods of microorganisms for different benzene derivatives varied. The maximum degradation rates of TCE for phenol-, benzoic acid-, toluene-, aniline- and chlorobenzene-grown aerobic sludge were 0.020, 0.017, 0.016, 0.0089 and 0.0047 mg g SS(-1) h(-1), respectively. The kinetic of TCE degradation in the absence of benzene derivative followed Monod equation well. Also, eight phyla were observed in the acclimated benzene derivative-grown aerobic sludge. Each of benzene derivative-grown aerobic sludge had different microbial community composition. This study can hopefully add new knowledge to the area of TCE co-metabolic by mixed microbial communities, and further the understanding on the function and applicability of aerobic-activated sludge.

  7. Relating Nutrient Uptake And Respiration With Metabolically Active Transient Storage

    NASA Astrophysics Data System (ADS)

    Argerich, A.; Haggerty, R.; Christensen, C.

    2009-12-01

    Quantification of water transient storage zones is critical to understand stream nutrient uptake, but the common method to measure transient storage parameters (based on the use of conservative solutes as hydrologic tracers) does not allow distinguishing among different transient storage compartments that contribute in different proportions to nutrient uptake. We use an alternative experimental approach, the Resazurin (Raz) “smart” tracer, which in combination with a conservative tracer is expected to give the relation between metabolically active transient storage (MATS) versus whole transient storage. Raz is a weakly fluorescent phenoxazine dye that undergoes an irreversible reduction to highly fluorescent Resorufin (hereafter referred as Rru) in the presence of aerobic respiration. We conducted a combined injection of Raz, NaCl, NH4, and PO4 in WS01 at H.J. Andrews Experimental Forest. The injection was performed during low-baseflow conditions (Q<0.5 L/s) at a constant flow rate for 5 days. Changes in time in EC, Raz, Rru and nutrient concentrations were examined at 3 surface sampling sites and at 6 wells. Simultaneously to the injection we measured whole-reach metabolism and we performed an SF6 injection to measure the exchange coefficient of O2 between the atmosphere and stream water. The reach achieved plateau conditions in less than 15 hours after the injection began and recovered to pre-injection conditions 56 hours after the end of the injection. EC corrected by background conditions decreased with distance reflecting a dilution effect caused by the water gaining condition of the reach. Raz concentration increased and Rru concentration decreased along the reach reflecting the transformation of Raz to Rru with distance. The Rru to Raz ratio at surface water was correlated with instantaneous rates of net ecosystem production (NEP) measured over the whole reach. Percentage of surface water in wells during plateau ranged between 50% and 95%. Raz

  8. Metabolism of platelet activating factor (PAF) by rabbit renal homogenates

    SciTech Connect

    Cagen, L.M.; Yeh, Y.M.; Baer, P.G.

    1986-05-01

    Rabbit renal cortical slices convert added (alkyl-/sup 3/H)-PAF to metabolites that cochromatograph with lyso-PAF and alkyl-acyl glycerophosphocholine (AAGPC) and to a tritiated nonpolar metabolite that is the principal product recovered from the tissues. Rabbit renal cortical homogenates convert mixtures of (alkyl-/sup 3/H)-PAF and (choline-/sup 14/C)-PAF to products that cochromatograph with lyso-PAF and with AAGPC and to a tritiated nonpolar and a /sup 14/C-labeled polar metabolite. Formation of the latter products follow parallel time courses; they are the principal species present after extended incubation (30 min). Enzymatic capacity for formation of these metabolites is concentrated in the microsomal fraction (100,000 x g pellet). Their formation by washed microsomes does not require the addition of cofactors, but their rate of formation is enhanced in the presence of high concentrations of Ca/sup + +/ (1mM) and abolished by EDTA (1.25mM) or EGTA (1.25mM). Formation of the polar metabolite does not appear to be due to phospholipase C or D activity. Its formation is not enhanced by addition of glutathione or 2-amino-6,7-dimethyl-tetrahydropteridine, cofactors that support oxidative dealkylation of alkyl ether phospholipids in other tissues. Conversion of PAF to final products other than AAGPC appears to be a significant pathway for disposition of this substance in rabbit kidney.

  9. The effect of essential oils of dietary wormwood (Artemisia princeps), with and without added vitamin E, on oxidative stress and some genes involved in cholesterol metabolism.

    PubMed

    Chung, Mi Ja; Kang, Ah-Young; Park, Sung-Ok; Park, Kuen-Woo; Jun, Hee-Jin; Lee, Sung-Joon

    2007-08-01

    Wormwood (Artemisia princeps) due to the abundance of antioxidant in its essential oils (EO), has been used as a traditional drug and health food in Korea. Oxidative stress plays an important role in the etiology of atherosclerosis thus antioxidative chemicals improves hepatic lipid metabolism partly by reducing oxysterol formation. The antioxidant activity was assessed using two methods, human low-density lipoprotein (LDL) oxidation and the anti-DPPH free radical assays. It was found that the antioxidant activity of EO with vitamin E higher than EO alone. To study mechanisms accounting for the antiatherosclerotic properties of this wormwood EO, we examined the expression of key genes in cholesterol metabolism such as the LDL receptor, the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and sterol regulatory element binding proteins. The induction was increased up to twofold at 0.05 mg/mL of EO treatment in HepG2 cells for 24h. When EO (0.2 mg/mL) was co-incubated with vitamin E, interestingly, the LDL receptor was dramatically induced by 5-6-folds. HMG-CoA reductase did not change. However, treatment with the higher concentration resulted in cytotoxicity. Our data suggest that wormwood EO with vitamin E may be anti-atherogenic due to their inhibition of LDL oxidation and upregulation of the LDL receptor.

  10. Model-driven multi-omic data analysis elucidates metabolic immunomodulators of macrophage activation

    PubMed Central

    Bordbar, Aarash; Mo, Monica L; Nakayasu, Ernesto S; Schrimpe-Rutledge, Alexandra C; Kim, Young-Mo; Metz, Thomas O; Jones, Marcus B; Frank, Bryan C; Smith, Richard D; Peterson, Scott N; Hyduke, Daniel R; Adkins, Joshua N; Palsson, Bernhard O

    2012-01-01

    Macrophages are central players in immune response, manifesting divergent phenotypes to control inflammation and innate immunity through release of cytokines and other signaling factors. Recently, the focus on metabolism has been reemphasized as critical signaling and regulatory pathways of human pathophysiology, ranging from cancer to aging, often converge on metabolic responses. Here, we used genome-scale modeling and multi-omics (transcriptomics, proteomics, and metabolomics) analysis to assess metabolic features that are critical for macrophage activation. We constructed a genome-scale metabolic network for the RAW 264.7 cell line to determine metabolic modulators of activation. Metabolites well-known to be associated with immunoactivation (glucose and arginine) and immunosuppression (tryptophan and vitamin D3) were among the most critical effectors. Intracellular metabolic mechanisms were assessed, identifying a suppressive role for de-novo nucleotide synthesis. Finally, underlying metabolic mechanisms of macrophage activation are identified by analyzing multi-omic data obtained from LPS-stimulated RAW cells in the context of our flux-based predictions. Our study demonstrates metabolism's role in regulating activation may be greater than previously anticipated and elucidates underlying connections between activation and metabolic effectors. PMID:22735334

  11. [TV, overweight and nutritional surveillance. Ads content, food intake and physical activity].

    PubMed

    Spagnoli, T D; Bioletti, L; Bo, C; Formigatti, M

    2003-01-01

    The relationship between television viewing and obesity in children and adults was examined in a large number of cross-sectional epidemiological studies. Some randomised, controlled trials confirmed the evidence that television viewing is a cause of increased body fatness. It seems of utility in nutritional surveillance to esteem time spent by children and adults in television watching and to evaluate ads contents and food preferences suggested by them. This editorial shows a two-years long analysis of food commercials broadcasted by the main Italian TV networks; food ads targeted on children, housewives and sport fans were evaluated; the relationship between television viewing, commercials and food intake or global lifestyle was investigated in a Piedmont's population (from Northern Italy). School projects aimed to reduce television viewing represent a promising strategy for preventing childhood obesity. PMID:14969315

  12. Metabolic control in a state of decreased activation: modulation of red cell metabolism.

    PubMed

    Jevning, R; Wilson, A F; Pirkle, H; O'Halloran, J P; Walsh, R N

    1983-11-01

    Very little is known in depth of the biochemical and physiological changes induced at the cellular level by human behavioral states. For study of the physiology of behavior at this level, the erythrocyte may be useful, because it is readily available and its metabolism and metabolic control are comparatively well understood. In this report we describe a marked decline of red cell glycolytic rate induced by the transcendental meditation technique (TM). This decline was significantly correlated with decreased plasma lactate concentration and with relaxation as indicated by electrodermal response. The occurrence of sleep was not correlated with the metabolic changes. The observed lack of variation of blood pH, blood gases, glucose, and hematocrit in this behavior implies that the decrease of erythrocyte metabolism is not an epiphenomenon of respiratory change or substrate availability. Based upon further measurements indicating persisting alteration of the red blood cell, we suggest the possibility of attachment of a humoral agent(s) to the cell in the mechanism of this effect. This behavioral effect is unique, and the effector(s) responsible may increase our understanding of metabolic control of the erythrocyte and of TM.

  13. Tidal switch on metabolic activity: Salinity induced responses on bacterioplankton metabolic capabilities in a tropical estuary

    NASA Astrophysics Data System (ADS)

    Thottathil, Shoji D.; Balachandran, K. K.; Jayalakshmy, K. V.; Gupta, G. V. M.; Nair, Shanta

    2008-07-01

    "Biolog" plates were used to study the changes in the metabolic capabilities of bacterioplankton over a complete tidal cycle in a tropical ecosystem (Cochin Estuary) along southwest coast of India. The pattern of utilization of carbon sources showed a definite shift in the community metabolism along a salinity gradient. Multivariate statistical analysis revealed two communities, namely allochthonous bacterioplankton sensitive to salinity and autochthonous bacterioplankton, which are tolerant to wide salinity fluctuations. Regression analysis showed salinity as the most important parameter influencing the physiological profile of bacterioplankton, irrespective of tide. Apart from salinity, limno-tolerant retrievable counts and halo-tolerant retrievable counts also accounted for the metabolic variation of bacterioplankton during low and high tides, respectively. The shift in the substrate utilization from carbohydrates to amino acids appears to be due to the physiological adaptation or nitrogen limitation of bacterial community with increasing salinity.

  14. Physical Activity and Sedentary Behavior Associated with Components of Metabolic Syndrome among People in Rural China

    PubMed Central

    Xiao, Jing; Shen, Chong; Chu, Min J.; Gao, Yue X.; Xu, Guang F.; Huang, Jian P.; Xu, Qiong Q.; Cai, Hui

    2016-01-01

    Background Metabolic syndrome is prevalent worldwide and its prevalence is related to physical activity, race, and lifestyle. Little data is available for people living in rural areas of China. In this study we examined associations of physical activity and sedentary behaviors with metabolic syndrome components among people in rural China. Methods The Nantong Metabolic Syndrome Study recruited 13,505 female and 6,997 male participants between 2007 and 2008. Data of socio-demographic characteristics and lifestyle were collected. The associations of physical activity and sedentary behaviors with metabolic syndrome components were analyzed. Results Prevalence of metabolic syndrome was 21.6%. It was significantly lower in men than in women. Low risks of metabolic syndrome were observed in those who did less sitting and engaged in more vigorous physical activity. The highest tertile of vigorous physical activity was associated with 15–40% decreased odds of metabolic syndrome and all of its components, except for low high-density lipoprotein cholesterol in men. Women with the highest tertile of moderate physical activity had 15–30% lower odds of central obesity, high glucose, and high triglycerides compared with those in the lowest tertile. Sitting time >42 hours per week had a 4%-12% attributable risk of metabolic syndrome, central obesity, and high triglycerides in both genders, and abnormal glucose and diastolic blood pressure in women. Sleeping for more than 8 hours per day was associated with risk of high serum glucose and lipids. Conclusions Our data suggested that physical activity has a preventive effect against metabolic syndrome and all its abnormal components, and that longer sitting time and sleep duration are associated with an increased risk of metabolic syndrome components, including central obesity and high triglycerides, glucose, and diastolic blood pressure. This study could provide information for future investigation into these associations. Also

  15. The mouse liver displays daily rhythms in the metabolism of phospholipids and in the activity of lipid synthesizing enzymes.

    PubMed

    Gorné, Lucas D; Acosta-Rodríguez, Victoria A; Pasquaré, Susana J; Salvador, Gabriela A; Giusto, Norma M; Guido, Mario Eduardo

    2015-02-01

    The circadian system involves central and peripheral oscillators regulating temporally biochemical processes including lipid metabolism; their disruption leads to severe metabolic diseases (obesity, diabetes, etc). Here, we investigated the temporal regulation of glycerophospholipid (GPL) synthesis in mouse liver, a well-known peripheral oscillator. Mice were synchronized to a 12:12 h light-dark (LD) cycle and then released to constant darkness with food ad libitum. Livers collected at different times exhibited a daily rhythmicity in some individual GPL content with highest levels during the subjective day. The activity of GPL-synthesizing/remodeling enzymes: phosphatidate phosphohydrolase 1 (PAP-1/lipin) and lysophospholipid acyltransferases (LPLATs) also displayed significant variations, with higher levels during the subjective day and at dusk. We evaluated the temporal regulation of expression and activity of phosphatidylcholine (PC) synthesizing enzymes. PC is mainly synthesized through the Kennedy pathway with Choline Kinase (ChoK) as a key regulatory enzyme or through the phosphatidylethanolamine (PE) N-methyltransferase (PEMT) pathway. The PC/PE content ratio exhibited a daily variation with lowest levels at night, while ChoKα and PEMT mRNA expression displayed maximal levels at nocturnal phases. Our results demonstrate that mouse liver GPL metabolism oscillates rhythmically with a precise temporal control in the expression and/or activity of specific enzymes.

  16. Managing daily intensive care activities: An observational study concerning ad hoc decision making of charge nurses and intensivists

    PubMed Central

    2011-01-01

    Introduction Management of daily activities in ICUs is challenging. ICU shift leaders, charge nurses and intensivists have to make several immediate ad hoc decisions to enable the fluent flow of ICU activities. Even though the management of ICU activities is quite well delineated by international consensus guidelines, we know only a little about the content of the real clinical decision making of ICU shift leaders. Methods We conducted an observational study with the think-aloud technique to describe the ad hoc decision making of ICU shift leaders. The study was performed in two university-affiliated hospital ICUs. Twelve charge nurses and eight intensivists were recruited. Observations were recorded and transcribed for qualitative content analysis using the protocol analysis method. The software program NVivo 7 was used to manage the data. The interrater agreement was assessed with percentages and by Cohen's κ. Results We identified 463 ad hoc decisions made by the charge nurses and 444 made by the intensivists. During our data collection time, this breaks down to over 230 immediately made decisions per day (24 hours). We divided the ad hoc decision making of ICU shift leaders into two types: process-focused and situation-focused. Process-focused decision making included more permanent information, such as human resources, know-how and material resources, whereas situation-focused decision making included decisions about single events, such as patient admission. We named eight different categories for ICU ad hoc decision making: (1) adverse events, (2) diagnostics, (3) human resources and know-how, (4) material resources, (5) patient admission, (6) patient discharge, (7) patient information and vital signs and (8) special treatments. Conclusions ICU shift leaders make a great number of complex ad hoc decisions throughout the day. Often this decision making involves both intensivists and charge nurses. It forms a bundle that requires versatile, immediate

  17. Sustainable development of tyre char-based activated carbons with different textural properties for value-added applications.

    PubMed

    Hadi, Pejman; Yeung, Kit Ying; Guo, Jiaxin; Wang, Huaimin; McKay, Gordon

    2016-04-01

    This paper aims at the sustainable development of activated carbons for value-added applications from the waste tyre pyrolysis product, tyre char, in order to make pyrolysis economically favorable. Two activation process parameters, activation temperature (900, 925, 950 and 975 °C) and residence time (2, 4 and 6 h) with steam as the activating agent have been investigated. The textural properties of the produced tyre char activated carbons have been characterized by nitrogen adsorption-desorption experiments at -196 °C. The activation process has resulted in the production of mesoporous activated carbons confirmed by the existence of hysteresis loops in the N2 adsorption-desorption curves and the pore size distribution curves obtained from BJH method. The BET surface area, total pore volume and mesopore volume of the activated carbons from tyre char have been improved to 732 m(2)/g, 0.91 cm(3)/g and 0.89 cm(3)/g, respectively. It has been observed that the BET surface area, mesopore volume and total pore volume increased linearly with burnoff during activation in the range of experimental parameters studied. Thus, yield-normalized surface area, defined as the surface area of the activated carbon per gram of the precursor, has been introduced to optimize the activation conditions. Accordingly, the optimized activation conditions have been demonstrated as an activation temperature of 975 °C and an activation time of 4 h.

  18. Sustainable development of tyre char-based activated carbons with different textural properties for value-added applications.

    PubMed

    Hadi, Pejman; Yeung, Kit Ying; Guo, Jiaxin; Wang, Huaimin; McKay, Gordon

    2016-04-01

    This paper aims at the sustainable development of activated carbons for value-added applications from the waste tyre pyrolysis product, tyre char, in order to make pyrolysis economically favorable. Two activation process parameters, activation temperature (900, 925, 950 and 975 °C) and residence time (2, 4 and 6 h) with steam as the activating agent have been investigated. The textural properties of the produced tyre char activated carbons have been characterized by nitrogen adsorption-desorption experiments at -196 °C. The activation process has resulted in the production of mesoporous activated carbons confirmed by the existence of hysteresis loops in the N2 adsorption-desorption curves and the pore size distribution curves obtained from BJH method. The BET surface area, total pore volume and mesopore volume of the activated carbons from tyre char have been improved to 732 m(2)/g, 0.91 cm(3)/g and 0.89 cm(3)/g, respectively. It has been observed that the BET surface area, mesopore volume and total pore volume increased linearly with burnoff during activation in the range of experimental parameters studied. Thus, yield-normalized surface area, defined as the surface area of the activated carbon per gram of the precursor, has been introduced to optimize the activation conditions. Accordingly, the optimized activation conditions have been demonstrated as an activation temperature of 975 °C and an activation time of 4 h. PMID:26775155

  19. Metabolic Profiles and Genetic Diversity of Denitrifying Communities in Activated Sludge after Addition of Methanol or Ethanol†

    PubMed Central

    Hallin, Sara; Throbäck, Ingela Noredal; Dicksved, Johan; Pell, Mikael

    2006-01-01

    External carbon sources can enhance denitrification rates and thus improve nitrogen removal in wastewater treatment plants. The effects of adding methanol and ethanol on the genetic and metabolic diversity of denitrifying communities in activated sludge were compared using a pilot-scale plant with two parallel lines. A full-scale plant receiving the same municipal wastewater, but without external carbon source addition, was the reference. Metabolic profiles obtained from potential denitrification rates with 10 electron donors showed that the denitrifying communities altered their preferences for certain compounds after supplementation with methanol or ethanol and that methanol had the greater impact. Clone libraries of nirK and nirS genes, encoding the two different nitrite reductases in denitrifiers, revealed that methanol also increased the diversity of denitrifiers of the nirS type, which indicates that denitrifiers favored by methanol were on the rise in the community. This suggests that there might be a niche differentiation between nirS and nirK genotypes during activated sludge processes. The composition of nirS genotypes also varied greatly among all samples, whereas the nirK communities were more stable. The latter was confirmed by denaturing gradient gel electrophoresis of nirK communities on all sampling occasions. Our results support earlier hypotheses that the compositions of denitrifier communities change during predenitrification processes when external carbon sources are added, although no severe effect could be observed from an operational point of view. PMID:16885297

  20. Activation of CAR and PXR by Dietary, Environmental and Occupational Chemicals Alters Drug Metabolism, Intermediary Metabolism, and Cell Proliferation

    PubMed Central

    Hernandez, J.P.; Mota, L.C.; Baldwin, W.S.

    2010-01-01

    The constitutive androstane receptor (CAR) and the pregnane × receptor (PXR) are activated by a variety of endogenous and exogenous ligands, such as steroid hormones, bile acids, pharmaceuticals, and environmental, dietary, and occupational chemicals. In turn, they induce phase I–III detoxification enzymes and transporters that help eliminate these chemicals. Because many of the chemicals that activate CAR and PXR are environmentally-relevant (dietary and anthropogenic), studies need to address whether these chemicals or mixtures of these chemicals may increase the susceptibility to adverse drug interactions. In addition, CAR and PXR are involved in hepatic proliferation, intermediary metabolism, and protection from cholestasis. Therefore, activation of CAR and PXR may have a wide variety of implications for personalized medicine through physiological effects on metabolism and cell proliferation; some beneficial and others adverse. Identifying the chemicals that activate these promiscuous nuclear receptors and understanding how these chemicals may act in concert will help us predict adverse drug reactions (ADRs), predict cholestasis and steatosis, and regulate intermediary metabolism. This review summarizes the available data on CAR and PXR, including the environmental chemicals that activate these receptors, the genes they control, and the physiological processes that are perturbed or depend on CAR and PXR action. This knowledge contributes to a foundation that will be necessary to discern interindividual differences in the downstream biological pathways regulated by these key nuclear receptors. PMID:20871735

  1. Metabolic, membrane, and functional responses of human polymorphonuclear leukocytes to platelet-activating factor.

    PubMed

    Ingraham, L M; Coates, T D; Allen, J M; Higgins, C P; Baehner, R L; Boxer, L A

    1982-06-01

    The phospholipid mediator of anaphylaxis, platelet-activating factor (PAF) is chemotactic for polymorphonuclear leukocytes (PMN). We have examined this agent's effects on several other PMN functions. Human PMN were prepared from heparinized venous blood by Ficoll gradient. Metabolic burst was examined by measurement of O2 use and O2.- production in the presence or absence of PAF (10(-6)--10(-9) M). Unless cells were treated with cytochalasin-B (5 micrograms/ml), no significant respiratory burst was demonstrated. However, pretreatment with PAF (10(-7) M) enhanced approximately threefold the O2 utilization found when cells were subsequently stimulated with 10(-7) M FMLP. PAF also stimulated arachidonic acid metabolism in 14C-arachidonic acid-labeled PMN. Thin-layer chromatography analysis of chloroform-methanol extracts showed substances that comigrated with authentic 5-hydroxyeicosatetraenoic acid had a marked increase in radioactivity following PAF stimulation at 10(-7) M. PAF failed to stimulate release of granule enzymes, B-glucuronidase, lysozyme, or myeloperoxidase unless cytochalasin-B were added. PAF from 10(-6) M to 10(-10) M affected PMN surface responses. PMN labeled with the fluorescent dye, chlorotetracycline, showed decreased fluorescence upon addition of PAF, suggesting translocation of membrane-bound cations. Further, the rate of migration of PMN in an electric field was decreased following PAF exposure, a change consistent with reduced cell surface charge. PMN self-aggregation and adherence to endothelial cells were both influenced by PAF (10(-6) M--10(-9) M). Aggregation was markedly stimulated by the compound, and the percent PMN adhering to endothelial cell monolayers increased almost twofold in the presence of 10(-8) M PAF. Thus, PAF promotes a variety of PMN responses: enhances respiratory burst, stimulates arachidonic acid turnover, alters cell membrane cation content and surface charge, and promotes PMN self-aggregation as well as adherence to

  2. Physical activity and metabolic risk among US youth: Mediation by obesity [abstract

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Physical activity has been inversely associated with metabolic risk, although pediatric studies are limited. It has been hypothesized that obesity mediates this relationship. Some studies reported that waist circumference (WC) is more highly related to metabolic risk than BMI, and may be a better me...

  3. Use of metabolic activation systems of tulip bulbs in the Ames test for environmental mutagens

    SciTech Connect

    Higashi, K.; Ikeuchi, K.; Karasaki, Y.

    1982-01-01

    The effects of trace amounts of PAH on the carcinogenesis in animals and human beings and on the ecology of plants are examined. An in vitro method has been developed which traces the metabolic fate of environmental mutagens in tulip bulbs. The method has been successful in confirming the presence of metabolic activation systems only for potent carcinogens. (JMT)

  4. Assessment of the activity of antiperspirants added to surgical hand disinfectants: methodological aspects and first observations.

    PubMed

    Pitten, F A; Rudolph, P; Below, H; Kramer, A

    2001-08-01

    Due to the risk of sensitization caused by glove powder, the use of unpowdered latex gloves is increasing. These unpowdered gloves need a special inner-surface layer which makes it easier for the applicant to put the glove on the hand and to remove it again. However, many users report difficulties with removing the gloves because of sweat production within the glove. Therefore, a method has been developed to evaluate the efficacy of antiperspirants which may be added either to the inner-surface layer of the glove or to hand disinfectants or to skin-care products used before the gloves are put on. The paper describes various trials to optimize this method. PMID:11759021

  5. Effects of petroleum on adrenocortical activity and on hepatic naphthalene-metabolizing activity in mallard ducks

    USGS Publications Warehouse

    Gorsline, J.; Holmes, W.N.

    1981-01-01

    Unstressed mallard ducks (Anas platyrhychos), given uncontaminated food and maintained on a short photoperiod, show two daily maxima in plasma corticosterone concentration ([B]); one occurring early in the light phase and a second just before the onset of darkness. After one week of exposure to food containing 3% (v/w) South Louisiana crude oil, plasma [B] were significantly lowered throughout the day. Similar abrupt declines in plasma [B] also occurred during the first 10 days of exposure to food containing 1% and 0.5% crude oil. Although the plasma [B] in birds consuming food contaminated with 0.5% crude oil increased between 10 and 50 days of exposure, the concentration after 50 days was still lower than normal. During the same interval, normal plasma [B] were restored in birds consuming food containing 1% and 3% crude oil. Significant increases occurred in the naphthalene-metabolizing properties of hepatic microsomes prepared from birds acutely exposed to all levels of petroleum-contaminated food and elevated levels were sustained throughout the first 50 days of exposure. Birds given food containing 3% crude oil for more than 50 days, however, showed steady declines in hepatic naphthalene-metabolizing activity. After 500 days, the activity was similar to that found in contemporaneous controls. During the same interval, the plasma [B] increased until the levels were higher than normal after 500 days of exposure; at this time, an inverse relationship, similar to that seen during the first week of exposure to contaminated food, was once more established between plasma [B] and the concomitant hepatic naphthalene-metabolizing activity.

  6. The metabolic activation and DNA adducts of dinitropyrenes.

    PubMed

    Beland, F A

    1986-08-01

    Dinitropyrenes are contaminants in diesel emissions that are mutagenic in bacteria and mammalian cells, and tumorigenic in laboratory animals. In this project, we investigated the factors that contributed to the extreme genotoxicity of dinitropyrenes in bacteria and determined if these factors were important in mammalian cells. Xanthine oxidase, a mammalian nitroreductase, catalyzed the conversion of the dinitropyrenes to DNA-bound products, but the level of binding did not exceed that observed with 1-nitropyrene. This suggested that factors in addition to nitroreduction were important in the metabolic activation of dinitropyrenes. 1-Nitro-6-nitrosopyrene and 1-nitro-8-nitrosopyrene were synthesized and reacted with DNA under reducing conditions. The same C8-substituted deoxyguanosine adducts were formed that were found in the xanthine oxidase-catalyzed reactions, which confirmed that incubation with this nitroreductase generated reactive N-hydroxy arylamine intermediates. In incubations with rat and human liver microsomes and cytosol, 1-nitropyrene and 1,3-dinitropyrene were reduced to a lesser extent than 1,6- and 1,8-dinitropyrene, which was in accord with their relative mutagenicities. Each of the cytosolic incubations were similar in that oxygen decreased aminopyrene, but not nitrosopyrene, formation. The data indicated that reduced derivatives of the nitrosopyrenes were redox cycling with oxygen, which decreased cytosolic aminopyrene formation. In cytosolic incubations, oxygen inhibited the reduction of 1-nitropyrene and 1,3-dinitropyrene to a greater extent than 1,6- and 1,8-dinitropyrene. By comparison, in microsomal investigations, the nitroreduction of each nitrated pyrene was equally oxygen-sensitive. This apparently was caused by the initial nitroanion radicals reacting with oxygen to decrease nitrosopyrene formation. Although more extensive nitroreduction of each compound was detected in anaerobic incubations, aerobic reduction of these compounds did

  7. Estrogenic activity of an environmental pollutant, 2-nitrofluorene, after metabolic activation by rat liver microsomes.

    PubMed

    Fujimoto, Takashi; Kitamura, Shigeyuki; Sanoh, Seigo; Sugihara, Kazumi; Yoshihara, Shin'ichi; Fujimoto, Nariaki; Ohta, Shigeru

    2003-04-01

    In this study, the metabolic activation of 2-nitrofluorene (NF) to estrogenic compounds was examined. NF was negative in estrogen reporter assays using estrogen-responsive yeast and human breast cancer cell line MCF-7. However, the compound exhibited estrogenic activity after incubation with liver microsomes of 3-methylcholanthrene-treated rats in the presence of NADPH. Minor estrogenic activity was observed when liver microsomes of untreated or phenobarbital-treated rats were used instead of those from 3-methylcholanthrene-treated rats. When the compound was incubated with the liver microsomes of 3-methylcholanthrene-treated rats in the presence of NADPH, 7-hydroxy-2-nitrofluorene (7-OH-NF) was formed as a major metabolite. However, little of the metabolite was formed by liver microsomes of untreated or phenobarbital-treated rats. Rat recombinant cytochrome P450 1A1 exhibited a significant oxidase activity toward NF, affording 7-OH-NF. Liver microsomes of phenobarbital-treated rats also enhanced oxidase activity toward NF. In this case, 9-hydroxy-2-nitrofluorene was formed. 7-OH-NF exhibited a significant estrogenic activity, while the activity of 9-hydroxy-2-nitrofluorene was much lower. These results suggest that the estrogenic activity of NF was due to formation of the 7-hydroxylated metabolite by liver microsomes. PMID:12659833

  8. Metabolic activities of five botryticides against Botrytis cinerea examined using the Biolog FF MicroPlate

    PubMed Central

    Wang, Hancheng; Wang, Jin; Li, Licui; Hsiang, Tom; Wang, Maosheng; Shang, Shenghua; Yu, Zhihe

    2016-01-01

    Tobacco grey mold caused by Botrytis cinerea is an important fungal disease worldwide. Boscalid, carbendazim, iprodione, pyrimethanil and propiconazole are representative botryticides for grey mold management. This research investigated the sensitivities of B. cinerea from tobacco to these chemicals using the Biolog FF Microplate. All five chemicals showed inhibitory activity, with average EC50 values of 0.94, 0.05, 0.50, 0.61 and 0.31 μg ml−1, respectively. B. cinerea metabolized 96.8% of tested carbon sources, including 29 effectively and 33 moderately, but the metabolic fingerprints differed under pressures imposed by these botryticides. For boscalid, B. cinerea was unable to metabolize many substrates related to tricarboxylic acid cycle. For carbendazim, carbon sources related to glycolysis were not metabolized. For iprodione, use of most carbon substrates was weakly inhibited, and the metabolic profile was similar to that of the control. For propiconazole, no carbon substrates were metabolized and the physiological and biochemical functions of the pathogen were totally inhibited. These findings provide useful information on metabolic activities of these botryticides, and may lead to future applications of the Biolog FF Microplate for examining metabolic effects of other fungicides on other fungi, as well as providing a metabolic fingerprint of B. cinerea that could be useful for identification. PMID:27491536

  9. Metabolic activities of five botryticides against Botrytis cinerea examined using the Biolog FF MicroPlate.

    PubMed

    Wang, Hancheng; Wang, Jin; Li, Licui; Hsiang, Tom; Wang, Maosheng; Shang, Shenghua; Yu, Zhihe

    2016-01-01

    Tobacco grey mold caused by Botrytis cinerea is an important fungal disease worldwide. Boscalid, carbendazim, iprodione, pyrimethanil and propiconazole are representative botryticides for grey mold management. This research investigated the sensitivities of B. cinerea from tobacco to these chemicals using the Biolog FF Microplate. All five chemicals showed inhibitory activity, with average EC50 values of 0.94, 0.05, 0.50, 0.61 and 0.31 μg ml(-1), respectively. B. cinerea metabolized 96.8% of tested carbon sources, including 29 effectively and 33 moderately, but the metabolic fingerprints differed under pressures imposed by these botryticides. For boscalid, B. cinerea was unable to metabolize many substrates related to tricarboxylic acid cycle. For carbendazim, carbon sources related to glycolysis were not metabolized. For iprodione, use of most carbon substrates was weakly inhibited, and the metabolic profile was similar to that of the control. For propiconazole, no carbon substrates were metabolized and the physiological and biochemical functions of the pathogen were totally inhibited. These findings provide useful information on metabolic activities of these botryticides, and may lead to future applications of the Biolog FF Microplate for examining metabolic effects of other fungicides on other fungi, as well as providing a metabolic fingerprint of B. cinerea that could be useful for identification. PMID:27491536

  10. Metabolic activities of five botryticides against Botrytis cinerea examined using the Biolog FF MicroPlate.

    PubMed

    Wang, Hancheng; Wang, Jin; Li, Licui; Hsiang, Tom; Wang, Maosheng; Shang, Shenghua; Yu, Zhihe

    2016-08-05

    Tobacco grey mold caused by Botrytis cinerea is an important fungal disease worldwide. Boscalid, carbendazim, iprodione, pyrimethanil and propiconazole are representative botryticides for grey mold management. This research investigated the sensitivities of B. cinerea from tobacco to these chemicals using the Biolog FF Microplate. All five chemicals showed inhibitory activity, with average EC50 values of 0.94, 0.05, 0.50, 0.61 and 0.31 μg ml(-1), respectively. B. cinerea metabolized 96.8% of tested carbon sources, including 29 effectively and 33 moderately, but the metabolic fingerprints differed under pressures imposed by these botryticides. For boscalid, B. cinerea was unable to metabolize many substrates related to tricarboxylic acid cycle. For carbendazim, carbon sources related to glycolysis were not metabolized. For iprodione, use of most carbon substrates was weakly inhibited, and the metabolic profile was similar to that of the control. For propiconazole, no carbon substrates were metabolized and the physiological and biochemical functions of the pathogen were totally inhibited. These findings provide useful information on metabolic activities of these botryticides, and may lead to future applications of the Biolog FF Microplate for examining metabolic effects of other fungicides on other fungi, as well as providing a metabolic fingerprint of B. cinerea that could be useful for identification.

  11. Quantifying interictal metabolic activity in human temporal lobe epilepsy

    SciTech Connect

    Henry, T.R.; Mazziotta, J.C.; Engel, J. Jr.; Christenson, P.D.; Zhang, J.X.; Phelps, M.E.; Kuhl, D.E. )

    1990-09-01

    The majority of patients with complex partial seizures of unilateral temporal lobe origin have interictal temporal hypometabolism on (18F)fluorodeoxyglucose positron emission tomography (FDG PET) studies. Often, this hypometabolism extends to ipsilateral extratemporal sites. The use of accurately quantified metabolic data has been limited by the absence of an equally reliable method of anatomical analysis of PET images. We developed a standardized method for visual placement of anatomically configured regions of interest on FDG PET studies, which is particularly adapted to the widespread, asymmetric, and often severe interictal metabolic alterations of temporal lobe epilepsy. This method was applied by a single investigator, who was blind to the identity of subjects, to 10 normal control and 25 interictal temporal lobe epilepsy studies. All subjects had normal brain anatomical volumes on structural neuroimaging studies. The results demonstrate ipsilateral thalamic and temporal lobe involvement in the interictal hypometabolism of unilateral temporal lobe epilepsy. Ipsilateral frontal, parietal, and basal ganglial metabolism is also reduced, although not as markedly as is temporal and thalamic metabolism.

  12. In-vitro suppression of metabolic activity in malignant human glioblastomas due to pulsed - low frequency electric potential exposures

    NASA Astrophysics Data System (ADS)

    Schlichting, Abby; Waynant, Ronald W.; Tata, Darrell B.

    2010-02-01

    The role of pulsed - low repetition frequency electric potential was investigated in suppressing the metabolic activities of aggressive human brain cancer cells. Twenty four hours post exposure the glioblastomas were found to be significantly inhibited in their metabolic activity. The findings herein reveal a near complete inhibition of glioblastoma's metabolic activity through selective applications of low frequency pulsed electric potentials.

  13. Natural compounds regulate energy metabolism by the modulating the activity of lipid-sensing nuclear receptors.

    PubMed

    Goto, Tsuyoshi; Kim, Young-Il; Takahashi, Nobuyuki; Kawada, Teruo

    2013-01-01

    Obesity causes excess fat accumulation in various tissues, most notoriously in the adipose tissue, along with other insulin-responsive organs such as skeletal muscle and the liver, which predisposes an individual to the development of metabolic abnormalities. The molecular mechanisms underlying obesity-induced metabolic abnormalities have not been completely elucidated; however, in recent years, the search for therapies to prevent the development of obesity and obesity-associated metabolic disorders has increased. It is known that several nuclear receptors, when activated by specific ligands, regulate carbohydrate and lipid metabolism at the transcriptional level. The expression of lipid metabolism-related enzymes is directly regulated by the activity of various nuclear receptors via their interaction with specific response elements in promoters of those genes. Many natural compounds act as ligands of nuclear receptors and regulate carbohydrate and lipid metabolism by regulating the activities of these nuclear receptors. In this review, we describe our current knowledge of obesity, the role of lipid-sensing nuclear receptors in energy metabolism, and several examples of food factors that act as agonists or antagonists of nuclear receptors, which may be useful for the management of obesity and the accompanying energy metabolism abnormalities.

  14. Farnesoid X receptor activation promotes cell proliferation via PDK4-controlled metabolic reprogramming

    PubMed Central

    Xie, Yang; Wang, Hong; Cheng, Xuefang; Wu, Yuzheng; Cao, Lijuan; Wu, Mengqiu; Xie, Wen; Wang, Guangji; Hao, Haiping

    2016-01-01

    Farnesoid X receptor (FXR) plays a pivotal role in the regulation of various metabolic pathways as well as liver regeneration. However, the casual link between cell proliferative effects during liver regeneration and metabolic regulation of FXR was elusive. In this study, we found that FXR activation significantly promotes HepG2 cell proliferation accompanied with metabolic switch towards the excessive accumulation of aerobic glycolytic intermediates including lactic acid, pyruvate and the subsequently increased biosynthesis of glycine. This FXR-induced metabolic switch was found dependent on an up-regulation of pyruvate dehydrogenate kinase 4 (PDK4), a FXR target gene. FXR agonists were found to promote liver regeneration in the murine model of APAP induced liver injury, which was associated with a metabolic switch favoring the accumulation of glycolytic intermediates as precursors for generation of biomass. However, FXR activation has little effect on the glycolytic metabolism in healthy primary hepatocytes in vitro and the liver of healthy mice in vivo. Therefore, we conclude that FXR may promote the proliferation of tumor cells and the hepatocytes in the process of liver regeneration by activating the PDK4-mediated metabolic reprogramming to generate glycolytic intermediates essential for rapid biomass generation, establishing a mechanistic link between cell proliferation and metabolic switch. PMID:26728993

  15. TNF-α-induced NF-κB activation stimulates skeletal muscle glycolytic metabolism through activation of HIF-1α.

    PubMed

    Remels, A H V; Gosker, H R; Verhees, K J P; Langen, R C J; Schols, A M W J

    2015-05-01

    A shift in quadriceps muscle metabolic profile toward decreased oxidative metabolism and increased glycolysis is a consistent finding in chronic obstructive pulmonary disease (COPD). Chronic inflammation has been proposed as a trigger of this pathological metabolic adaptation. Indeed, the proinflammatory cytokine TNF-α impairs muscle oxidative metabolism through activation of the nuclear factor-κB (NF-κB) pathway. Putative effects on muscle glycolysis, however, are unclear. We hypothesized that TNF-α-induced NF-κB signaling stimulates muscle glycolytic metabolism through activation of the glycolytic regulator hypoxia-inducible factor-1α (HIF-1α). Wild-type C2C12 and C2C12-IκBα-SR (blocked NF-κB signaling) myotubes were stimulated with TNF-α, and its effects on glycolytic metabolism and involvement of the HIF pathway herein were investigated. As proof of principle, expression of HIF signaling constituents was investigated in quadriceps muscle biopsies of a previously well-characterized cohort of clinically stable patients with severe COPD and healthy matched controls. TNF-α increased myotube glucose uptake and lactate production and enhanced the activity and expression levels of multiple effectors of muscle glycolytic metabolism in a NF-κB-dependent manner. In addition, TNF-α activated HIF signaling, which required classical NF-κB activation. Moreover, the knockdown of HIF-1α largely attenuated TNF-α-induced increases in glycolytic metabolism. Accordingly, the mRNA levels of HIF-1α and the HIF-1α target gene, vascular endothelial growth factor (VEGF), were increased in muscle biopsies of COPD patients compared with controls, which was most pronounced in the patients with high levels of muscle TNF-α. In conclusion, these data show that TNF-α-induced classical NF-κB activation enhances muscle glycolytic metabolism in a HIF-1α-dependent manner. PMID:25710281

  16. Metabolomics analysis of Cistus monspeliensis leaf extract on energy metabolism activation in human intestinal cells.

    PubMed

    Shimoda, Yoichi; Han, Junkyu; Kawada, Kiyokazu; Smaoui, Abderrazak; Isoda, Hiroko

    2012-01-01

    Energy metabolism is a very important process to improve and maintain health from the point of view of physiology. It is well known that the intracellular ATP production is contributed to energy metabolism in cells. Cistus monspeliensis is widely used as tea, spices, and medical herb; however, it has not been focusing on the activation of energy metabolism. In this study, C. monspeliensis was investigated as the food resources by activation of energy metabolism in human intestinal epithelial cells. C. monspeliensis extract showed high antioxidant ability. In addition, the promotion of metabolites of glycolysis and TCA cycle was induced by C. monspeliensis treatment. These results suggest that C. monspeliensis extract has an ability to enhance the energy metabolism in human intestinal cells.

  17. Metabolomics Analysis of Cistus monspeliensis Leaf Extract on Energy Metabolism Activation in Human Intestinal Cells

    PubMed Central

    Shimoda, Yoichi; Han, Junkyu; Kawada, Kiyokazu; Smaoui, Abderrazak; Isoda, Hiroko

    2012-01-01

    Energy metabolism is a very important process to improve and maintain health from the point of view of physiology. It is well known that the intracellular ATP production is contributed to energy metabolism in cells. Cistus monspeliensis is widely used as tea, spices, and medical herb; however, it has not been focusing on the activation of energy metabolism. In this study, C. monspeliensis was investigated as the food resources by activation of energy metabolism in human intestinal epithelial cells. C. monspeliensis extract showed high antioxidant ability. In addition, the promotion of metabolites of glycolysis and TCA cycle was induced by C. monspeliensis treatment. These results suggest that C. monspeliensis extract has an ability to enhance the energy metabolism in human intestinal cells. PMID:22523469

  18. Lack of leptin activity in blood samples of Adélie penguin and bar-tailed godwit.

    PubMed

    Yosefi, Sara; Hen, Gideon; Rosenblum, Charles I; Cerasale, David J; Beaulieu, Michaël; Criscuolo, Francois; Friedman-Einat, Miriam

    2010-10-01

    Unsuccessful attempts to identify the leptin gene in birds are well documented, despite the characterization of its receptor (LEPR). Since leptin and LEPR have poor sequence conservation among vertebrates, we speculated that a functional assay should represent the best way to detect leptin in birds. Using a leptin bioassay that is based on activation of the chicken LEPR in cultured cells, blood samples from wild birds with extreme seasonal variation in voluntary food intake and fat deposition (Adélie penguins and bar-tailed godwits) were tested for leptin activity. In these experiments, blood samples collected during the pre-incubation and the chick-rearing periods of Adélie penguins, and during the migratory flight and refueling stages of bar-tailed godwits, were found to contain no detectable leptin activity, while the sensitivity of the assay to activation by human blood samples from donor subjects representing a variety of body mass indices and fat contents was clearly demonstrated. These results suggest that in birds, an alternative control mechanism to that of mammals operates in the communication between the body fat tissues and the central control on energy homeostasis.

  19. The active metabolic rate predicts a male spider's proximity to females and expected fitness.

    PubMed

    Kasumovic, Michael M; Seebacher, Frank

    2013-04-23

    Conspicuous traits, such as weaponry and body size, are often correlated with fitness. By contrast, we understand less about how inconspicuous physiological traits affect fitness. Not only is linking physiology directly to fitness a challenge, but in addition, behavioural studies most often focus on resting or basal metabolic rates, resulting in a poor understanding of how active metabolic rates affect fitness. Here we use the golden orb-web spider (Nephila plumipes), a species for which proximity to a female on the web predicts a male's paternity share, to examine the role of resting and active metabolic rates in fitness. Using a semi-natural experimental set-up, we show that males closer to a female have higher active metabolic rates than males further from females. This higher metabolic activity is paralleled by increased citrate synthase activity, suggesting greater mitochondrial densities. Our results link both higher active metabolic rates and increased citrate synthase activity with fitness. Coupled with the behaviour and life history of N. plumipes, these results provide insight into the evolution of physiological systems.

  20. Substrate sources regulate spatial variation of metabolically active methanogens from two contrasting freshwater wetlands.

    PubMed

    Lin, Yongxin; Liu, Deyan; Ding, Weixin; Kang, Hojeong; Freeman, Chris; Yuan, Junji; Xiang, Jian

    2015-12-01

    There is ample evidence that methane (CH4) emissions from natural wetlands exhibit large spatial variations at a field scale. However, little is known about the metabolically active methanogens mediating these differences. We explored the spatial patterns in active methanogens of summer inundated Calamagrostis angustifolia marsh with low CH4 emissions and permanently inundated Carex lasiocarpa marsh with high CH4 emissions in Sanjiang Plain, China. In C. angustifolia marsh, the addition of (13)C-acetate significantly increased the CH4 production rate, and Methanosarcinaceae methanogens were found to participate in the consumption of acetate. In C. lasiocarpa marsh, there was no apparent increase in the CH4 production rate and no methanogen species were labeled with (13)C. When (13)CO2-H2 was added, however, CH4 production was found to be due to Fen Cluster (Methanomicrobiales) in C. angustifolia marsh and Methanobacterium Cluster B (Methanobacteriaceae) together with Fen Cluster in C. lasiocarpa marsh. These results suggested that CH4 was produced primarily by hydrogenotrophic methanogens using substrates mainly derived from plant litter in C. lasiocarpa marsh and by both hydrogenotrophic and acetoclastic methanogens using substrates mainly derived from root exudate in C. angustifolia marsh. The significantly lower CH4 emissions measured in situ in C. angustifolia marsh was primarily due to a deficiency of substrates compared to C. lasiocarpa marsh. Therefore, we speculate that the substrate source regulates both the type of active methanogens and the CH4 production pathway and consequently contributes to the spatial variations in CH4 productions observed in these freshwater marshes. PMID:26286511

  1. Drug activity screening based on microsomes-hydrogel system in predicting metabolism induced antitumor effect of oroxylin A

    PubMed Central

    Yang, Huiying; Li, Jianfeng; Zheng, Yuanting; Zhou, Lu; Tong, Shanshan; Zhao, Bei; Cai, Weimin

    2016-01-01

    A novel microsomes-hydrogel added cell culture system (MHCCS) was employed in the antitumor activity screening of natural compounds, aiming to achieve drug screening with better in vivo correlation, higher initiative to explore the potential active metabolites, and investigation of the antitumor mechanism from the perspective of metabolism. MTT assay and cell apoptosis detection showed that test drug oroxylin A (OA) had enhanced cytotoxicity and wogonin (W) with reduced cytotoxicity on MCF-7 cell line upon MHCCS incubation. In vivo antitumor evaluations also demonstrated that OA induced higher tumor inhibition than W at the same dosage. To explore the reasons, nine major metabolites of OA were separated and collected through UPLC-Q-TOF and semi-preparative HPLC. Metabolites M318 exhibited higher cytotoxicity than OA and other metabolites by MTT assay. 1H NMR spectrums, HPLC and TOF MS/MS results revealed that OA was catalyzed into its active metabolite M318 via a ring-opening reaction. M318 induced significant cell apoptosis and S-phase arrest through affecting tumor survival related genes after mechanism study. In conclusion, our MHCCS could be a useful tool for drug activity screening from a perspective of metabolism. PMID:26905263

  2. Patterns of metabolic activity in the treatment of schizophrenia

    SciTech Connect

    Brodie, J.D.; Christman, D.R.; Corona, J.F.; Fowler, J.S.; Gomez-Mont, F.; Jaeger, J.; Micheels, P.A.; Rotrosen, J.; Russell, J.A.; Volkow, N.D.; Wikler, A.

    1984-04-01

    Six patients with chronic schizophrenia were studied with positron emission tomography (PET) before and after neuroleptic treatment, using fluorine-18-labeled fluorodeoxyglucose. After treatment, the mean whole-slice glucose metabolic rate at the level of the basal ganglia showed a 25% increase. However, patterns of frontal hypometabolism observed with the schizophrenic patients were not altered by medication. Pattern analysis using the fast Fourier transform was applied to a set of 422 images from a mixed group of normal, depressed, and schizophrenic subjects. Reconstruction of the images with low-frequency coefficients was excellent, reducing considerably the number of variables needed to characterize each image. Hierarchical cluster analysis categorized the transformed images according to anatomical level and subject group (patient versus control). The results suggest the utility of this procedure for the classification and characterization of metabolic PET images from psychiatric patients. 8 references, 3 figures, 1 table.

  3. The spectrum of enzymes involved in activation of 2-aminoanthracene varies with the metabolic system applied.

    PubMed

    Veres, Zsuzsa; Török, Géza; Tóth, Eva; Vereczkey, László; Jemnitz, Katalin

    2005-09-01

    The aim of this study was to estimate the involvement of cytochrome P450s (CYPs) in the metabolic activation of 2-aminoanthracene (2AA) by use of metabolic systems such as liver S9 or hepatocytes from untreated and beta-naphthoflavone (BNF)- or phenobarbital (PB)-treated rats. Metabolic activation was determined in the Salmonella reverse mutation assay (Ames test). Unexpectedly, both enzyme inducers, BNF and PB, significantly decreased the mutagenicity of 2AA activated by S9 fractions. 2AA mutagenicity was detected in the presence of cytochrome P450 inhibitors such as alpha-naphthoflavone (ANF), clotrimazole and N-benzylimidazole to study the contribution of CYP isoenzymes to the activation process. ANF significantly decreased the activation of 2AA by S9 from untreated rats. In contrast, ANF significantly increased the metabolic activation of 2AA by S9 from BNF- and PB-treated rats. The enhanced mutagenicity was not altered by co-incubation with clotrimazole and ANF. Pre-incubation of 2AA in the presence of N-benzylimidazole significantly increased the activation of 2AA by S9 from BNF- and PB-treated rats, which suggests that CYPs play minor role in 2AA metabolic activation by rat liver S9 fractions. In contrast with the results described above, BNF treatment of rats significantly enhanced the activation of 2AA by hepatocytes. ANF attenuated the extent of this activation suggesting that different enzymes play a major role in the activation processes in these metabolic systems. Our results indicate that identification of mutagenic hazard by use of the Ames test may depend on the metabolic system applied.

  4. In vivo metabolic activity of hamster suprachiasmatic nuclei: use of anesthesia

    SciTech Connect

    Schwartz, W.J.

    1987-02-01

    In vivo glucose utilization was measured in the suprachiasmatic nuclei (SCN) of Golden hamsters using the /sup 14/C-labeled deoxyglucose technique. A circadian rhythm of SCN metabolic activity could be measured in this species, but only during pentobarbital sodium anesthesia when the surrounding background activity of adjacent hypothalamus was suppressed. Both the SCN's metabolic oscillation and its time-keeping ability are resistant to general anesthesia.

  5. Promoted degradation of perfluorooctanic acid by persulfate when adding activated carbon.

    PubMed

    Lee, Yu-Chi; Lo, Shang-Lien; Kuo, Jeff; Huang, Chin-Pao

    2013-10-15

    Treatment of persistent perfluorooctanoic acid (PFOA) in water using persulfate (PS) oxidation typically requires an elevated temperature or UV irradiation, which is energy-consuming. Under relatively low temperatures of 25-45°C, activated carbon (AC) activated PS oxidation of PFOA was evaluated for its potential of practical applications. With presence of AC in PS oxidation, PFOA removal efficiency at 25°C reached 682% with a high defluorination efficiency of 549% after 12h and few intermediates of short-chain perfluorinated carboxylic acids (PFCAs) were found. The removal and defluorination rates with the combined AC/PS system were approximately 12 and 19 times higher than those of the PS-only system, respectively. Activated carbon not only removes PFOA through adsorption, but also activates PS to form sulfate radicals that accelerate the decomposition and mineralization of PFOA. The activation energy for PS oxidation of PFOA was reduced from 668 to 261kJ/mol by the catalytic effect of AC, which implies a lower reaction temperature and a shorter reaction time would suffice. A 2-cycle schematic reaction mechanism was used to describe PS oxidation of PFOA with the generation of various intermediates and end-products.

  6. Metabolic Activity of Radish Sprouts Derived Isothiocyanates in Drosophila melanogaster.

    PubMed

    Baenas, Nieves; Piegholdt, Stefanie; Schloesser, Anke; Moreno, Diego A; García-Viguera, Cristina; Rimbach, Gerald; Wagner, Anika E

    2016-02-18

    We used Drosophila melanogaster as a model system to study the absorption, metabolism and potential health benefits of plant bioactives derived from radish sprouts (Raphanus sativus cv. Rambo), a Brassicaceae species rich in glucosinolates and other phytochemicals. Flies were subjected to a diet supplemented with lyophilized radish sprouts (10.6 g/L) for 10 days, containing high amounts of glucoraphenin and glucoraphasatin, which can be hydrolyzed by myrosinase to the isothiocyanates sulforaphene and raphasatin, respectively. We demonstrate that Drosophila melanogaster takes up and metabolizes isothiocyanates from radish sprouts through the detection of the metabolite sulforaphane-cysteine in fly homogenates. Moreover, we report a decrease in the glucose content of flies, an upregulation of spargel expression, the Drosophila homolog of the mammalian PPARγ-coactivator 1 α, as well as the inhibition of α-amylase and α-glucosidase in vitro. Overall, we show that the consumption of radish sprouts affects energy metabolism in Drosophila melanogaster which is reflected by lower glucose levels and an increased expression of spargel, a central player in mitochondrial biogenesis. These processes are often affected in chronic diseases associated with aging, including type II diabetes mellitus.

  7. Metabolic Activity of Radish Sprouts Derived Isothiocyanates in Drosophila melanogaster

    PubMed Central

    Baenas, Nieves; Piegholdt, Stefanie; Schloesser, Anke; Moreno, Diego A.; García-Viguera, Cristina; Rimbach, Gerald; Wagner, Anika E.

    2016-01-01

    We used Drosophila melanogaster as a model system to study the absorption, metabolism and potential health benefits of plant bioactives derived from radish sprouts (Raphanus sativus cv. Rambo), a Brassicaceae species rich in glucosinolates and other phytochemicals. Flies were subjected to a diet supplemented with lyophilized radish sprouts (10.6 g/L) for 10 days, containing high amounts of glucoraphenin and glucoraphasatin, which can be hydrolyzed by myrosinase to the isothiocyanates sulforaphene and raphasatin, respectively. We demonstrate that Drosophila melanogaster takes up and metabolizes isothiocyanates from radish sprouts through the detection of the metabolite sulforaphane-cysteine in fly homogenates. Moreover, we report a decrease in the glucose content of flies, an upregulation of spargel expression, the Drosophila homolog of the mammalian PPARγ-coactivator 1 α, as well as the inhibition of α-amylase and α-glucosidase in vitro. Overall, we show that the consumption of radish sprouts affects energy metabolism in Drosophila melanogaster which is reflected by lower glucose levels and an increased expression of spargel, a central player in mitochondrial biogenesis. These processes are often affected in chronic diseases associated with aging, including type II diabetes mellitus. PMID:26901196

  8. 1-Nitropyrene-metabolizing activities of fish liver preparations

    SciTech Connect

    Kitamura, S.; Tatsumi, K.

    1997-03-01

    Nitropolycyclic aromatic hydrocarbons, which are a new class of carcinogenic environmental pollutants, enter waterways by release of urban wastewater into the environment and by atmospheric fallout of airborne particles associated with smog. It is important to examine their metabolism not only in mammalian species but also in fish species for assessment of possible risk associated with human exposure to the pollutants. Recently, we examined the in vivo metabolism of 1-nitropyrene, a typical nitropolycyclic aromatic hydrocarbon, in fish focusing on nitroreduction and acylation. When goldfish were bathed in a solution of 1-nitropyrene or its reduction product 1-aminopyrne, one or two metabolites were isolated from the solution, respectively. The former metabolite was identified as 1-aminopyrene and the latter two metabolites as 1-acetylaminopyrene and 1-formylaminopyrene by comparing their mass and UV spectra, and behaviors in HPLC and TLC with those of authentic samples. In mammalian species, nitro-reduction followed by N-acetylation and N-formylation of nitropolycyclic aromatic hydrocarbons have been demonstrated with their liver preparations. To our knowledge, such metabolic reactions of nitropolycyclic aromatic hydrocarbons have not been studied with fish liver preparations. 15 refs., 2 figs., 1 tab.

  9. pH dependent antioxidant activity of lettuce (L. sativa) and synergism with added phenolic antioxidants.

    PubMed

    Altunkaya, Arzu; Gökmen, Vural; Skibsted, Leif H

    2016-01-01

    Influence of pH on the antioxidant activities of combinations of lettuce extract (LE) with quercetin (QC), green tea extract (GTE) or grape seed extract (GSE) was investigated for both reduction of Fremy's salt in aqueous solution using direct electron spin resonance (ESR) spectroscopy and in L-α-phosphatidylcholine liposome peroxidation assay measured following formation of conjugated dienes. All examined phenolic antioxidants showed increasing radical scavenging effect with increasing pH values by using both methods. QC, GTE and GSE acted synergistically in combination with LE against oxidation of peroxidating liposomes and with QC showing the largest effect. The pH dependent increase of the antioxidant activity of the phenols is due to an increase of their electron-donating ability upon deprotonation and to their stabilization in alkaline solutions leading to polymerization reaction. Such polymerization reactions of polyphenolic antioxidants can form new oxidizable -OH moieties in their polymeric products resulting in a higher radical scavenging activity.

  10. pH dependent antioxidant activity of lettuce (L. sativa) and synergism with added phenolic antioxidants.

    PubMed

    Altunkaya, Arzu; Gökmen, Vural; Skibsted, Leif H

    2016-01-01

    Influence of pH on the antioxidant activities of combinations of lettuce extract (LE) with quercetin (QC), green tea extract (GTE) or grape seed extract (GSE) was investigated for both reduction of Fremy's salt in aqueous solution using direct electron spin resonance (ESR) spectroscopy and in L-α-phosphatidylcholine liposome peroxidation assay measured following formation of conjugated dienes. All examined phenolic antioxidants showed increasing radical scavenging effect with increasing pH values by using both methods. QC, GTE and GSE acted synergistically in combination with LE against oxidation of peroxidating liposomes and with QC showing the largest effect. The pH dependent increase of the antioxidant activity of the phenols is due to an increase of their electron-donating ability upon deprotonation and to their stabilization in alkaline solutions leading to polymerization reaction. Such polymerization reactions of polyphenolic antioxidants can form new oxidizable -OH moieties in their polymeric products resulting in a higher radical scavenging activity. PMID:26212937

  11. Adding Value: Using On-Line Activities To Ensure Student Success.

    ERIC Educational Resources Information Center

    Richards, Griff; Fong, Rosamaria

    This paper describes a Web site containing activities for chemistry that aid student learning. Used as an adjunct to the normal classroom and laboratory sessions, instructional goals of the Web site were to provide guidance and encourage regular and timely study. Initially learners were able to review the weekly objectives, see short explanations…

  12. Student Activism -- and Involvement in the Educational Program. Federation AdHoc Committee Report, January, 1970.

    ERIC Educational Resources Information Center

    New Jersey State Federation of District Boards of Education, Trenton.

    This report notes that (1) activism is preferable to apathy, (2) larger problems loom for schools that fail to involve parents and community, (3) board member and administrator rigidity can cause conflict, and (4) black and Spanish-speaking students have special problems. Recommendations for school administrators and teachers emphasize sincerity…

  13. Improvements to the FATOLA computer program including added actively controlled landing gear subroutines

    NASA Technical Reports Server (NTRS)

    Mall, G. H.

    1983-01-01

    Modifications to a multi-degree-of-freedom flexible aircraft take-off and landing analysis (FATOLA) computer program, including a provision for actively controlled landing gears to expand the programs simulation capabilities, are presented. Supplemental instructions for preparation of data and for use of the modified program are included.

  14. The Perception of Communication Related Value-Added Educational Activities: A Survey of Graduate Business Students

    ERIC Educational Resources Information Center

    Barker, Randolph T.; Stowers, Robert H.

    2007-01-01

    The purpose of this article is to evaluate value-add methods and activities applied to organizational communication college-level course work. Graduate organizational communication faculty are aware that their classes serve as direct preparation for students entering business and professional careers. The knowledge learned and the skills acquired…

  15. Hairy AdS solitons

    NASA Astrophysics Data System (ADS)

    Anabalón, Andrés; Astefanesei, Dumitru; Choque, David

    2016-11-01

    We construct exact hairy AdS soliton solutions in Einstein-dilaton gravity theory. We examine their thermodynamic properties and discuss the role of these solutions for the existence of first order phase transitions for hairy black holes. The negative energy density associated to hairy AdS solitons can be interpreted as the Casimir energy that is generated in the dual filed theory when the fermions are antiperiodic on the compact coordinate.

  16. Activities of key metabolic enzymes in the heater organs of scombroid fishes.

    PubMed

    Tullis, A; Block, B A; Sidell, B D

    1991-11-01

    Maximal in vitro activities of key metabolic enzymes were measured in brain and eye heaters of five species of scombroid fishes. Istiophorid billfishes (blue marlin, striped marlin and Mediterranean spearfish), xiphiid billfishes (Pacific and Mediterranean stocks) and a scombrid fish (butterfly mackerel) were included in the analysis. Our main objectives were (1) to assess the maximum possible substrate flux in heater tissue, and (2) to determine what metabolic substrates could fuel heat production. Heater tissue of all scombroids examined showed extremely high oxidative capacity. Activities of citrate synthase, a commonly measured index of oxidative metabolism, included the highest value ever reported for vertebrate tissue. In most billfishes, citrate synthase activities were similar to or higher than those found for mammalian cardiac and avian flight muscle. Marker enzymes for aerobic carbohydrate metabolism (hexokinase) and fatty acid metabolism (carnitine palmitoyltransferase and 3-hydroxyacyl-CoA dehydrogenase) also displayed extraordinarily high activities. Activities of carnitine palmitoyltransferase measured in heater organs were among the highest reported for vertebrates. These results indicate that heat production could be fueled aerobically by either lipid or carbohydrate metabolism. Inter- and intraspecifically, heater organs of fishes from the colder Mediterranean waters had a higher aerobic capacity and, hence, a greater heat-generating potential, than fishes from the warmer waters of the Pacific. This difference may be attributed to different thermal environments or it may result from allometry, since fishes caught in the Mediterranean were considerably smaller than those caught in the Pacific.

  17. Sustained Axenic Metabolic Activity by the Obligate Intracellular Bacterium Coxiella burnetii▿ †

    PubMed Central

    Omsland, Anders; Cockrell, Diane C.; Fischer, Elizabeth R.; Heinzen, Robert A.

    2008-01-01

    Growth of Coxiella burnetii, the agent of Q fever, is strictly limited to colonization of a viable eukaryotic host cell. Following infection, the pathogen replicates exclusively in an acidified (pH 4.5 to 5) phagolysosome-like parasitophorous vacuole. Axenic (host cell free) buffers have been described that activate C. burnetii metabolism in vitro, but metabolism is short-lived, with bacterial protein synthesis halting after a few hours. Here, we describe a complex axenic medium that supports sustained (>24 h) C. burnetii metabolic activity. As an initial step in medium development, several biological buffers (pH 4.5) were screened for C. burnetii metabolic permissiveness. Based on [35S]Cys-Met incorporation, C. burnetii displayed optimal metabolic activity in citrate buffer. To compensate for C. burnetii auxotrophies and other potential metabolic deficiencies, we developed a citrate buffer-based medium termed complex Coxiella medium (CCM) that contains a mixture of three complex nutrient sources (neopeptone, fetal bovine serum, and RPMI cell culture medium). Optimal C. burnetii metabolism occurred in CCM with a high chloride concentration (140 mM) while the concentrations of sodium and potassium had little effect on metabolism. CCM supported prolonged de novo protein and ATP synthesis by C. burnetii (>24 h). Moreover, C. burnetii morphological differentiation was induced in CCM as determined by the transition from small-cell variant to large-cell variant. The sustained in vitro metabolic activity of C. burnetii in CCM provides an important tool to investigate the physiology of this organism including developmental transitions and responses to antimicrobial factors associated with the host cell. PMID:18310349

  18. Effect of dietary sodium phytate and microbial phytase on the lipase activity and lipid metabolism of broiler chickens.

    PubMed

    Liu, Ning; Ru, Yingjun; Wang, Jianping; Xu, Tingsheng

    2010-03-01

    The objective of the present study was to investigate the effect of dietary phytate and microbial phytase on the lipase activity, lipid metabolism and mRNA expressions of fatty acid synthase (FASN) and leptin in broiler chickens. The study was conducted as a 2 x 3 factorial arrangement of treatments with phytate phosphorus at 0.20 and 0.40 % (added as the sodium phytate) and supplemental microbial phytase at 0, 500, or 1000 phytase units/kg. The results showed that phytase improved (P < 0.05) the growth performance and ileal digestibility of nutrients of broilers, but phytate had no effect (P>0.05) on these parameters, except the decrease (P < 0.01) in the digestibility of Ca. Phytate decreased (P < 0.05) the lipase activity, serum total cholesterol (T-CHO) and hepatic TAG, and elevated (P < 0.01) serum NEFA and HDL cholesterol. Phytase decreased (P < 0.05) serum NEFA, but increased (P < 0.01) serum T-CHO and hepatic TAG. Phytate and phytase also influenced (P < 0.01) the mRNA expressions of leptin in the liver. There were significant (P < 0.05) interactions of phytate and phytase on the concentrations of serum TAG and LDL cholesterol, hepatic NEFA and T-CHO, and the mRNA expressions of FASN. The results suggest that phytate and phytase can affect lipase activity and lipid metabolism of broiler chickens.

  19. Exposure of organic extracts of air particulates to sunlight leads to metabolic activation independence for mutagenicity.

    PubMed

    al-Khodairy, F; Hannan, M A

    1997-06-13

    Air particulates were collected on Whatman, GFA glass fibre filters using a RADECO constant-flow air sampler from a car-parking basement and an open roadside adjacent to the basement. While the basement was not exposed to sunlight, the roadside from where air samples were collected was exposed to regular daylight in the month of July (peak summer month). The filters were soaked and sonicated in acetone to dislodge the particulates and then a residue was obtained after evaporation of acetone. The residues were either held in dark or exposed to natural sunlight or germicidal UV light before being tested for mutagenicity using the Salmonella tester strain TA98 with and without metabolic activation (S9 mix). The results showed that the addition of S9 mix resulted in only a slight increase in the frequency of histidine revertants/plate in the case of daylight-exposed roadside air samples. On the other hand, a considerable increase in mutagenicity was observed in the case of the basement air samples, particularly at higher concentrations of the organic extracts when S9 mix was added. However, a pre-exposure of the organic extract of air from the basement to sunlight abrogated the need for S9 mix for showing mutagenic activity. A pre-exposure of the same extracts to germicidal UV light failed to produce a similar effect. These results suggested that long wavelengths of natural sunlight could be responsible for the conversion of certain promutagens in air particulates into direct-acting mutagens. The environmental impact of solar radiation as a modifier of air particulate mutagens in high-sun countries like Saudi Arabia needs to be carefully considered for assessment of air pollution-related health risks. PMID:9219550

  20. Studies on polyamine and ornithine metabolism in rat colon: effects of two synergistically. Acting inducers of ornithine decarboxylase activity

    SciTech Connect

    Stanley, B.A.

    1987-01-01

    Ornithine decarboxylase (ODC) activity in rat colon mucosa was determined by the release of /sup 14/CO/sub 2/ from radiolabeled ornithine in the presence (total enzyme) or absence (holoenzyme) of added pyridoxal-5'-phosphate (PLP). Total leucine incorporation into acid-precipitable protein over 30 minute was calculated by dividing the /sup 3/H-leucine in protein by the specific activity of the intracellular leucine. Amino acids, polyamines, and PLP-semicarbazide were quantified by high pressure liquid chromatography. Ornithine aminotransaminase activity (OAT) was measured as the quantity of pyrolline (5-carboxy) produced from alpha-ketoglutarate and ornithine. After 10 weeks on a high or no vitamin B/sub 6/ diet, no change in basal ODC activity was seen; however, sodium deoxycholate instillation in vitamin B/sub 6/ deficient rats led to a large increase in total but not holo-ODC activity. In rats fed normal chow diet, no increases in mucosal PLP levels were seen after either treatment. Increases in general protein synthesis rate could not account for the peaks in ODC activity after either stimulus. Putrescine increases were proportional to peaks of ODC activity after either stimulus, while spermine levels remained depressed for 18 hours after starvation/refeeding. Ornithine levels were increased after either stimulus, and this increase was linked to decreases in OAT activity, indicating short-term coordination of overall ornithine metabolism to favor polyamine biosynthesis.

  1. Temporal repeatability of metabolic rate and the effect of organ mass and enzyme activity on metabolism in European eel (Anguilla anguilla).

    PubMed

    Boldsen, Martin Maagaard; Norin, Tommy; Malte, Hans

    2013-05-01

    Intraspecific variation in metabolic rate of fish can be pronounced and have been linked to various fitness-related behavioural and physiological traits, but the underlying causes for this variation have received far less attention than the consequences of it. In the present study we investigated whether European eels (Anguilla anguilla) displayed temporal repeatability of body-mass-corrected (residual) metabolic rate over a two-month period and if variations in organ mass and enzyme activity between individual fish could be the cause for the observed variation in metabolic rate. Both standard metabolic rate (SMR; Pearson's r=0.743) and routine metabolic rate (RMR; r=0.496) were repeatable over the two-month period. Repeatability of RMR is an interesting finding as it indicates that the level of spontaneous activity in respirometer-confined fish is not random. Cumulative organ mass (liver, heart, spleen and intestine; mean 1.6% total body mass) was found to explain 38% of the variation in SMR (r=0.613) with the liver (one of the metabolically most active organs) being the driver for the correlation between organ mass and metabolic rate. No relationships were found for either liver citrate synthase or cytochrome oxidase activity and metabolic rate in the European eels. Reasons for, and contributions to, the observed variation in metabolic rate are discussed.

  2. Biological activity of all-trans retinol requires metabolic conversion to all-trans retinoic acid and is mediated through activation of nuclear retinoid receptors in human keratinocytes.

    PubMed

    Kurlandsky, S B; Xiao, J H; Duell, E A; Voorhees, J J; Fisher, G J

    1994-12-30

    The biological activity of all-trans retinol, in human keratinocytes, was investigated through metabolic and functional analyses that assessed the capacity for retinol uptake and metabolism and the mechanism of retinol-induced activation of gene transcription. Human keratinocytes converted all-trans retinol predominantly to retinyl esters, which accounted for 60 and 90% of cell-associated radiolabel after a 90-min pulse and a 48-h chase, respectively. Human keratinocytes also metabolized all-trans retinol to low levels of all-trans retinoic acid (11.47-131.3 ng/mg of protein) in a dose-dependent manner, between 0.3 and 10 microM added retinol. Small amounts of 13-cis retinoic acid (5.47-8.62 ng/mg of protein) were detected, but 9-cis retinoic acid was detected only when keratinocytes were incubated with radiolabeled retinol. There was no accumulation of the oxidized catabolic metabolites 4-hydroxy- or 4-oxoretinoic acid; however, 5,6-epoxy retinoic acid was detected at pharmacological levels (10 and 30 microM) of added retinol. Biological activity of retinol was assessed through analysis of two known retinoic acid-mediated responses: 1) reduction of type I epidermal transglutaminase and 2) activation of a retinoic acid receptor-dependent reporter gene, beta RARE3-tk-CAT. Both all-trans retinol and all-trans retinoic acid reduced type I epidermal transglutaminase in a dose-dependent manner; however, the ED50 for all-trans retinol (10 nM) was 10 times greater than for all-trans retinoic acid (1 nM). All-trans retinol also stimulated beta RARE3-tk-CAT reporter gene activity in a dose-dependent manner. Half-maximal induction was observed at 30 nM retinol, which was again 10-fold greater than observed with all-trans retinoic acid. Cotransfection of human keratinocytes with expression vectors for dominant negative mutant retinoic acid and retinoid X receptors reduced retinol-induced beta RARE3-tk-CAT reporter gene activation by 80%. Inhibition of conversion of all

  3. [Need for rheologically active, vasoactive and metabolically active substances in the initial treatment of acute acoustic trauma].

    PubMed

    Pilgramm, M; Schumann, K

    1986-10-01

    Two rheologically active and 8 vasoactive and metabolically active substances were compared in eight independent studies, some of which were randomised and double blind, on 400 patients who had suffered acute acoustic trauma. The control group was given saline. Spontaneous recovery was excluded as far as possible. The following substances were tested: Dextran 40, hydroxyethyl starch 40/0.5, naftidrofurylhydrogenoxalate, Vinpocetin, betahistine, pentoxifylline, flunaricine, Regeneresen AU 4 and 0.9% saline. All groups showed superior results to the control group in both long-term and short-term tests with respect to hearing gain and tinnitis improvement. The rheologically effective substances showed no statistically significant variations. None of the vasoactive or metabolically active substances used as adjunctive therapy improved the results achieved with rheologically effective substances alone. These results demonstrate that acute acoustic trauma can be most effectively treated by rheologically active substances; vasoactive and metabolically active substances are unnecessary. Hyperbaric oxygenation is advantageous as an adjunctive therapy. PMID:2432041

  4. Polyphosphate - an ancient energy source and active metabolic regulator

    PubMed Central

    2011-01-01

    There are a several molecules on Earth that effectively store energy within their covalent bonds, and one of these energy-rich molecules is polyphosphate. In microbial cells, polyphosphate granules are synthesised for both energy and phosphate storage and are degraded to produce nucleotide triphosphate or phosphate. Energy released from these energetic carriers is used by the cell for production of all vital molecules such as amino acids, nucleobases, sugars and lipids. Polyphosphate chains directly regulate some processes in the cell and are used as phosphate donors in gene regulation. These two processes, energetic metabolism and regulation, are orchestrated by polyphosphate kinases. Polyphosphate kinases (PPKs) can currently be categorized into three groups (PPK1, PPK2 and PPK3) according their functionality; they can also be divided into three groups according their homology (EcPPK1, PaPPK2 and ScVTC). This review discusses historical information, similarities and differences, biochemical characteristics, roles in stress response regulation and possible applications in the biotechnology industry of these enzymes. At the end of the review, a hypothesis is discussed in view of synthetic biology applications that states polyphosphate and calcium-rich organelles have endosymbiotic origins from ancient protocells that metabolized polyphosphate. PMID:21816086

  5. Influence of temperature and activity on the metabolic rate of adult Drosophila melanogaster.

    PubMed

    Berrigan, D; Partridge, L

    1997-12-01

    We measured metabolic rates of adult male Drosophila melanogaster allowed to evolve in the laboratory at 18 and 25 degrees C and compared these with measurements of metabolic rates of flies collected along a latitudinal gradient in Australia. Metabolic rates of flies that had evolved in the laboratory at low temperature were 5-7% higher than those of flies allowed to evolve at high temperature. Metabolic rates of field collected increased with latitude when measured at 18 degrees C but not at higher temperature (25 degrees C) and were about 9% greater in high latitude (approximately 41'00) flies than low latitude (16'53) flies. Metabolic rate was strongly influenced by measurement temperature; estimated Q10s ranged from 1.79 to 2.5 for measurements made at 18 and 25 degrees C. Metabolic rate scaled isometrically with body mass; the estimated slope of a ln-ln regression of metabolic rate and body mass was 1.03 +/- 0.1. We used our measures of metabolic rate and activity to estimate the minimum cost of transport (MCOT) while walking. The estimates of MCOT have high standard errors (lab, 34.30 +/- 14.2 ml O2/g/km; and field, 38.0 +/- 17.0 ml O2/g/km); however, they differ by only 3-9% from predicted values based on allometric relationships reported in the literature.

  6. Role of the AMP-activated protein kinase in regulating fatty acid metabolism during exercise.

    PubMed

    Steinberg, Gregory R

    2009-06-01

    During moderate-intensity exercise, fatty acids are the predominant substrate for working skeletal muscle. The release of fatty acids from adipose tissue stores, combined with the ability of skeletal muscle to actively fine tune the gradient between fatty acid and carbohydrate metabolism, depending on substrate availability and energetic demands, requires a coordinated system of metabolic control. Over the past decade, since the discovery that AMP-activated protein kinase (AMPK) was increased in accordance with exercise intensity, there has been significant interest in the proposed role of this ancient stress-sensing kinase as a critical integrative switch controlling metabolic responses during exercise. In this review, studies examining the role of AMPK as a regulator of fatty acid metabolism in both adipose tissue and skeletal muscle during exercise will be discussed. Exercise induces activation of AMPK in adipocytes and regulates triglyceride hydrolysis and esterfication through phosphorylation of hormone sensitive lipase (HSL) and glycerol-3-phosphate acyl-transferase, respectively. In skeletal muscle, exercise-induced activation of AMPK is associated with increases in fatty acid uptake, phosphorylation of HSL, and increased fatty acid oxidation, which is thought to occur via the acetyl-CoA carboxylase-malony-CoA-CPT-1 signalling axis. Despite the importance of AMPK in regulating fatty acid metabolism under resting conditions, recent evidence from transgenic models of AMPK deficiency suggest that alternative signalling pathways may also be important for the control of fatty acid metabolism during exercise.

  7. Leisure-time exercise, physical activity during work and commuting, and risk of metabolic syndrome.

    PubMed

    Kuwahara, Keisuke; Honda, Toru; Nakagawa, Tohru; Yamamoto, Shuichiro; Akter, Shamima; Hayashi, Takeshi; Mizoue, Tetsuya

    2016-09-01

    Data are limited regarding effect of intensity of leisure-time physical activity on metabolic syndrome. Furthermore, no prospective data are available regarding effect of occupational and commuting physical activity on metabolic syndrome. We compared metabolic syndrome risk by intensity level of leisure-time exercise and by occupational and commuting physical activity in Japanese workers. We followed 22,383 participants, aged 30-64 years, without metabolic syndrome until 2014 March (maximum, 5 years of follow-up). Physical activity was self-reported. Metabolic syndrome was defined by the Joint Statement criteria. We used Cox regression models to estimate the hazard ratios (HRs) and 95 % confidence intervals (CIs) of metabolic syndrome. During a mean follow-up of 4.1 years, 5361 workers developed metabolic syndrome. After adjustment for covariates, compared with engaging in no exercise, the HRs (95 % CIs) for <7.5, 7.5 to <16.5, and ≥16.5 metabolic equivalent hours of exercise per week were 0.99 (0.90, 1.08), 0.99 (0.90, 1.10), and 0.95 (0.83, 1.08), respectively, among individuals engaging in moderate-intensity exercise alone; 0.93 (0.75, 1.14), 0.81 (0.64, 1.02), and 0.84 (0.66, 1.06), among individuals engaging in vigorous-intensity exercise alone; and 0.90 (0.70, 1.17), 0.74 (0.62, 0.89), and 0.81 (0.69, 0.96) among individuals engaging in the two intensities. Higher occupational physical activity was weakly but significantly associated with lower risk of metabolic syndrome. Walking to and from work was not associated with metabolic syndrome. Vigorous-intensity exercise alone or vigorous-intensity combined with moderate-intensity exercise and worksite intervention for physical activity may help prevent metabolic syndrome for Japanese workers.

  8. Metabolic Syndrome Remodels Electrical Activity of the Sinoatrial Node and Produces Arrhythmias in Rats

    PubMed Central

    Albarado-Ibañez, Alondra; Avelino-Cruz, José Everardo; Velasco, Myrian; Torres-Jácome, Julián; Hiriart, Marcia

    2013-01-01

    In the last ten years, the incidences of metabolic syndrome and supraventricular arrhythmias have greatly increased. The metabolic syndrome is a cluster of alterations, which include obesity, hypertension, hypertriglyceridemia, glucose intolerance and insulin resistance, that increase the risk of developing, among others, atrial and nodal arrhythmias. The aim of this study is to demonstrate that metabolic syndrome induces electrical remodeling of the sinus node and produces arrhythmias. We induced metabolic syndrome in 2-month-old male Wistar rats by administering 20% sucrose in the drinking water. Eight weeks later, the rats were anesthetized and the electrocardiogram was recorded, revealing the presence of arrhythmias only in treated rats. Using conventional microelectrode and voltage clamp techniques, we analyzed the electrical activity of the sinoatrial node. We observed that in the sinoatrial node of “metabolic syndrome rats”, compared to controls, the spontaneous firing of all cells decreased, while the slope of the diastolic depolarization increased only in latent pacemaker cells. Accordingly, the pacemaker currents If and Ist increased. Furthermore, histological analysis showed a large amount of fat surrounding nodal cardiomyocytes and a rise in the sympathetic innervation. Finally, Poincaré plot denoted irregularity in the R-R and P-P ECG intervals, in agreement with the variability of nodal firing potential recorded in metabolic syndrome rats. We conclude that metabolic syndrome produces a dysfunction SA node by disrupting normal architecture and the electrical activity, which could explain the onset of arrhythmias in rats. PMID:24250786

  9. Persistent Organic Pollutants Modify Gut Microbiota–Host Metabolic Homeostasis in Mice Through Aryl Hydrocarbon Receptor Activation

    PubMed Central

    Zhang, Limin; Nichols, Robert G.; Correll, Jared; Murray, Iain A.; Tanaka, Naoki; Smith, Philip B.; Hubbard, Troy D.; Sebastian, Aswathy; Albert, Istvan; Hatzakis, Emmanuel; Gonzalez, Frank J.; Perdew, Gary H.

    2015-01-01

    , Hubbard TD, Sebastian A, Albert I, Hatzakis E, Gonzalez FJ, Perdew GH, Patterson AD. 2015. Persistent organic pollutants modify gut microbiota–host metabolic homeostasis in mice through aryl hydrocarbon receptor activation. Environ Health Perspect 123:679–688; http://dx.doi.org/10.1289/ehp.1409055 PMID:25768209

  10. Whole-organism screening for gluconeogenesis identifies activators of fasting metabolism.

    PubMed

    Gut, Philipp; Baeza-Raja, Bernat; Andersson, Olov; Hasenkamp, Laura; Hsiao, Joseph; Hesselson, Daniel; Akassoglou, Katerina; Verdin, Eric; Hirschey, Matthew D; Stainier, Didier Y R

    2013-02-01

    Improving the control of energy homeostasis can lower cardiovascular risk in metabolically compromised individuals. To identify new regulators of whole-body energy control, we conducted a high-throughput screen in transgenic reporter zebrafish for small molecules that modulate the expression of the fasting-inducible gluconeogenic gene pck1. We show that this in vivo strategy identified several drugs that affect gluconeogenesis in humans as well as metabolically uncharacterized compounds. Most notably, we find that the translocator protein ligands PK 11195 and Ro5-4864 are glucose-lowering agents despite a strong inductive effect on pck1 expression. We show that these drugs are activators of a fasting-like energy state and, notably, that they protect high-fat diet-induced obese mice from hepatosteatosis and glucose intolerance, two pathological manifestations of metabolic dysregulation. Thus, using a whole-organism screening strategy, this study has identified new small-molecule activators of fasting metabolism.

  11. Metaproteomics: extracting and mining proteome information to characterize metabolic activities in microbial communities.

    PubMed

    Abraham, Paul E; Giannone, Richard J; Xiong, Weili; Hettich, Robert L

    2014-01-01

    Contemporary microbial ecology studies usually employ one or more "omics" approaches to investigate the structure and function of microbial communities. Among these, metaproteomics aims to characterize the metabolic activities of the microbial membership, providing a direct link between the genetic potential and functional metabolism. The successful deployment of metaproteomics research depends on the integration of high-quality experimental and bioinformatic techniques for uncovering the metabolic activities of a microbial community in a way that is complementary to other "meta-omic" approaches. The essential, quality-defining informatics steps in metaproteomics investigations are: (1) construction of the metagenome, (2) functional annotation of predicted protein-coding genes, (3) protein database searching, (4) protein inference, and (5) extraction of metabolic information. In this article, we provide an overview of current bioinformatic approaches and software implementations in metaproteome studies in order to highlight the key considerations needed for successful implementation of this powerful community-biology tool.

  12. Metaproteomics: extracting and mining proteome information to characterize metabolic activities in microbial communities.

    PubMed

    Abraham, Paul E; Giannone, Richard J; Xiong, Weili; Hettich, Robert L

    2014-01-01

    Contemporary microbial ecology studies usually employ one or more "omics" approaches to investigate the structure and function of microbial communities. Among these, metaproteomics aims to characterize the metabolic activities of the microbial membership, providing a direct link between the genetic potential and functional metabolism. The successful deployment of metaproteomics research depends on the integration of high-quality experimental and bioinformatic techniques for uncovering the metabolic activities of a microbial community in a way that is complementary to other "meta-omic" approaches. The essential, quality-defining informatics steps in metaproteomics investigations are: (1) construction of the metagenome, (2) functional annotation of predicted protein-coding genes, (3) protein database searching, (4) protein inference, and (5) extraction of metabolic information. In this article, we provide an overview of current bioinformatic approaches and software implementations in metaproteome studies in order to highlight the key considerations needed for successful implementation of this powerful community-biology tool. PMID:24939130

  13. Intracellular coenzymes as natural biomarkers for metabolic activities and mitochondrial anomalies.

    PubMed

    Heikal, Ahmed A

    2010-04-01

    Mitochondria play a pivotal role in energy metabolism, programmed cell death and oxidative stress. Mutated mitochondrial DNA in diseased cells compromises the structure of key enzyme complexes and, therefore, mitochondrial function, which leads to a myriad of health-related conditions such as cancer, neurodegenerative diseases, diabetes and aging. Early detection of mitochondrial and metabolic anomalies is an essential step towards effective diagnoses and therapeutic intervention. Reduced nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) play important roles in a wide range of cellular oxidation-reduction reactions. Importantly, NADH and FAD are naturally fluorescent, which allows noninvasive imaging of metabolic activities of living cells and tissues. Furthermore, NADH and FAD autofluorescence, which can be excited using distinct wavelengths for complementary imaging methods and is sensitive to protein binding and local environment. This article highlights recent developments concerning intracellular NADH and FAD as potential biomarkers for metabolic and mitochondrial activities.

  14. Breast Cancer Metabolism and Mitochondrial Activity: The Possibility of Chemoprevention with Metformin.

    PubMed

    Cazzaniga, Massimiliano; Bonanni, Bernardo

    2015-01-01

    Metabolic reprogramming refers to the ability of cancer cells to alter their metabolism in order to support the increased energy request due to continuous growth, rapid proliferation, and other characteristics typical of neoplastic cells. It has long been believed that the increase of metabolic request was independent of the mitochondrial action but recently we know that mitochondrial activity together with metabolism plays a pivotal role in the regulation of the energy needed for tumor cell growth and proliferation. For these reasons the mitochondria pathways could be a new target for therapeutic and chemopreventive intervention. Metformin in particular is actually considered a promising agent against mitochondrial activity thanks to its ability to inhibit the mitochondrial complex I. PMID:26605341

  15. Metaproteomics: extracting and mining proteome information to characterize metabolic activities in microbial communities

    SciTech Connect

    Abraham, Paul E; Giannone, Richard J; Xiong, Weili; Hettich, Robert {Bob} L

    2014-01-01

    Contemporary microbial ecology studies usually employ one or more omics approaches to investigate the structure and function of microbial communities. Among these, metaproteomics aims to characterize the metabolic activities of the microbial membership, providing a direct link between the genetic potential and functional metabolism. The successful deployment of metaproteomics research depends on the integration of high-quality experimental and bioinformatic techniques for uncovering the metabolic activities of a microbial community in a way that is complementary to other meta-omic approaches. The essential, quality-defining informatics steps in metaproteomics investigations are: (1) construction of the metagenome, (2) functional annotation of predicted protein-coding genes, (3) protein database searching, (4) protein inference, and (5) extraction of metabolic information. In this article, we provide an overview of current bioinformatic approaches and software implementations in metaproteome studies in order to highlight the key considerations needed for successful implementation of this powerful community-biology tool.

  16. Interferon-γ regulates cellular metabolism and mRNA translation to potentiate macrophage activation.

    PubMed

    Su, Xiaodi; Yu, Yingpu; Zhong, Yi; Giannopoulou, Eugenia G; Hu, Xiaoyu; Liu, Hui; Cross, Justin R; Rätsch, Gunnar; Rice, Charles M; Ivashkiv, Lionel B

    2015-08-01

    Interferon-γ (IFN-γ) primes macrophages for enhanced microbial killing and inflammatory activation by Toll-like receptors (TLRs), but little is known about the regulation of cell metabolism or mRNA translation during this priming. We found that IFN-γ regulated the metabolism and mRNA translation of human macrophages by targeting the kinases mTORC1 and MNK, both of which converge on the selective regulator of translation initiation eIF4E. Physiological downregulation of mTORC1 by IFN-γ was associated with autophagy and translational suppression of repressors of inflammation such as HES1. Genome-wide ribosome profiling in TLR2-stimulated macrophages showed that IFN-γ selectively modulated the macrophage translatome to promote inflammation, further reprogram metabolic pathways and modulate protein synthesis. These results show that IFN-γ-mediated metabolic reprogramming and translational regulation are key components of classical inflammatory macrophage activation.

  17. Breast Cancer Metabolism and Mitochondrial Activity: The Possibility of Chemoprevention with Metformin

    PubMed Central

    Cazzaniga, Massimiliano; Bonanni, Bernardo

    2015-01-01

    Metabolic reprogramming refers to the ability of cancer cells to alter their metabolism in order to support the increased energy request due to continuous growth, rapid proliferation, and other characteristics typical of neoplastic cells. It has long been believed that the increase of metabolic request was independent of the mitochondrial action but recently we know that mitochondrial activity together with metabolism plays a pivotal role in the regulation of the energy needed for tumor cell growth and proliferation. For these reasons the mitochondria pathways could be a new target for therapeutic and chemopreventive intervention. Metformin in particular is actually considered a promising agent against mitochondrial activity thanks to its ability to inhibit the mitochondrial complex I. PMID:26605341

  18. Flexibility in metabolic rate and activity level determines individual variation in overwinter performance.

    PubMed

    Auer, Sonya K; Salin, Karine; Anderson, Graeme J; Metcalfe, Neil B

    2016-11-01

    Energy stores are essential for the overwinter survival of many temperate and polar animals, but individuals within a species often differ in how quickly they deplete their reserves. These disparities in overwinter performance may be explained by differences in their physiological and behavioral flexibility in response to food scarcity. However, little is known about whether individuals exhibit correlated or independent changes in these traits, and how these phenotypic changes collectively affect their winter energy use. We examined individual flexibility in both standard metabolic rate and activity level in response to food scarcity and their combined consequences for depletion of lipid stores among overwintering brown trout (Salmo trutta). Metabolism and activity tended to decrease, yet individuals exhibited striking differences in their physiological and behavioral flexibility. The rate of lipid depletion was negatively related to decreases in both metabolic and activity rates, with the smallest lipid loss over the simulated winter period occurring in individuals that had the greatest reductions in metabolism and/or activity. However, changes in metabolism and activity were negatively correlated; those individuals that decreased their SMR to a greater extent tended to increase their activity rates, and vice versa, suggesting among-individual variation in strategies for coping with food scarcity.

  19. Topically applied oxymetazoline. Ocular vasoconstrictive activity, pharmacokinetics, and metabolism.

    PubMed

    Duzman, E; Anderson, J; Vita, J B; Lue, J C; Chen, C C; Leopold, I H

    1983-07-01

    Two double-blind, random-assignment clinical trials demonstrated the effectiveness of topical oxymetazoline hydrochloride in reducing histamine-induced hyperemia. Oxymetazoline hydrochloride at an optimum strength of 0.025% produced a marked and prolonged reduction of hyperemia, with the onset of effect occurring within one to five minutes of instillation. Safety indicators, including BP, heart rate, intraocular pressure, pupil size, and visual acuity, did not change significantly from baseline values. Oxymetazoline was absorbed slowly into the eye: only 0.006% of the original drug concentration was found in the aqueous humors of rabbits 30 minutes after instillation; the balance remained primarily in external ocular tissues. Metabolic studies in rabbits indicated that excreted amounts of unmetabolized radioactive oxymetazoline in urine following drug administration were similar (23%) for the ocular and nasal routes of application. The proportions of oxymetazoline metabolite to unchanged oxymetazoline were constant for all administration routes tested.

  20. The added value of a European Union tuberculosis reference laboratory network--analysis of the national reference laboratory activities.

    PubMed

    Drobniewski, F A; Nikolayevskyy, V; Hoffner, S; Pogoryelova, O; Manissero, D; Ozin, A J

    2008-03-18

    National reference laboratories (NRL) and other laboratories are the cornerstones of well-functioning tuberculosis programmes and surveillance activities. However, the scope and activity of NRL services for mycobacterial identification and drug susceptibility testing (DST) has not been examined in detail across the European Union (EU), nor has the added value of cooperation and networking at the European level been explored with regard to strengthening laboratory services. Therefore, the European Centre for Disease Prevention and Control (ECDC) has commissioned a survey to explore these issues and to identify areas of work that could bring added value by supporting networking activities of tuberculosis (TB) reference laboratories in the EU. Structured questionnaires were sent to TB reference laboratory experts in the EU and European Economic Area (EEA) countries, and in three additional countries selected on the basis of their networking activities with EU projects and other initiatives (Switzerland, Croatia and Israel). The compiled results describe the activities and structure of 32 NRLs (29 countries replied, a response rate of 91%). The analysis of the survey led to the following recommendations for strengthening TB laboratory services: (1) implementing of the published European standards for TB laboratory services with respect to infrastructure, national reference functions, biosafety, human resources, quality assurance, operational research (including evaluation of new medical diagnostics), accuracy and speed, appropriately trained staff; (2) ensuring that laboratories only perform activities for which they have demonstrated proficiency; (3) implement validated and standardised second-line drug susceptibility testing (DST), including drugs used to define extensively drug-resistant tuberculosis (XDR TB); (4) aiming to identify Mycobacterium tuberculosis complex (MTBC) and rifampicin (RIF) resistance in over 90% of cultures and cases from smear-positive sputum

  1. Antioxidant and antimicrobial activity of Kitaibelia vitifolia extract as alternative to the added nitrite in fermented dry sausage.

    PubMed

    Kurćubić, Vladimir S; Mašković, Pavle Z; Vujić, Jelena M; Vranić, Danijela V; Vesković-Moračanin, Slavica M; Okanović, Đorđe G; Lilić, Slobodan V

    2014-08-01

    Fermented dry sausages (FDS) without nitrite added, fortified with bioactive phenol and flavonoid compounds originating from the ethanol extract of Kitaibelia vitifolia were food matrix for investigation of its antioxidant and antimicrobial potency. These activities were researched in order to improve the sausages' shelf-life, safety, and provide health benefits to consumers as well. The oxidative stability of the FDS, containing two different levels of natural preservative, was evaluated using five different contemporary methods for antioxidative activity. The activity was tested on the 20th day of the refrigerated storage. Minimum inhibitory concentrations of the sausage extract were determined against six microorganisms, using a micro dilution method. Determined optimal effective concentration of dissolved K. vitifolia extract (12.5 g/kg of meat dough) revealed strong antioxidant activity, and moderate antimicrobial activity against Escherichia coli (minimum inhibitory concentrations=15.625 μg/mL). The modified sausages had typical chemical-physical characteristics of FDS, controlled on 0, 13, 26 d of ripening and 20, 40 and 60 d of storage.

  2. Value Added?

    ERIC Educational Resources Information Center

    UCLA IDEA, 2012

    2012-01-01

    Value added measures (VAM) uses changes in student test scores to determine how much "value" an individual teacher has "added" to student growth during the school year. Some policymakers, school districts, and educational advocates have applauded VAM as a straightforward measure of teacher effectiveness: the better a teacher, the better students…

  3. Integration of light and metabolic signals for stem cell activation at the shoot apical meristem

    PubMed Central

    Pfeiffer, Anne; Janocha, Denis; Dong, Yihan; Medzihradszky, Anna; Schöne, Stefanie; Daum, Gabor; Suzaki, Takuya; Forner, Joachim; Langenecker, Tobias; Rempel, Eugen; Schmid, Markus; Wirtz, Markus; Hell, Rüdiger; Lohmann, Jan U

    2016-01-01

    A major feature of embryogenesis is the specification of stem cell systems, but in contrast to the situation in most animals, plant stem cells remain quiescent until the postembryonic phase of development. Here, we dissect how light and metabolic signals are integrated to overcome stem cell dormancy at the shoot apical meristem. We show on the one hand that light is able to activate expression of the stem cell inducer WUSCHEL independently of photosynthesis and that this likely involves inter-regional cytokinin signaling. Metabolic signals, on the other hand, are transduced to the meristem through activation of the TARGET OF RAPAMYCIN (TOR) kinase. Surprisingly, TOR is also required for light signal dependent stem cell activation. Thus, the TOR kinase acts as a central integrator of light and metabolic signals and a key regulator of stem cell activation at the shoot apex. DOI: http://dx.doi.org/10.7554/eLife.17023.001 PMID:27400267

  4. Integration of light and metabolic signals for stem cell activation at the shoot apical meristem.

    PubMed

    Pfeiffer, Anne; Janocha, Denis; Dong, Yihan; Medzihradszky, Anna; Schöne, Stefanie; Daum, Gabor; Suzaki, Takuya; Forner, Joachim; Langenecker, Tobias; Rempel, Eugen; Schmid, Markus; Wirtz, Markus; Hell, Rüdiger; Lohmann, Jan U

    2016-01-01

    A major feature of embryogenesis is the specification of stem cell systems, but in contrast to the situation in most animals, plant stem cells remain quiescent until the postembryonic phase of development. Here, we dissect how light and metabolic signals are integrated to overcome stem cell dormancy at the shoot apical meristem. We show on the one hand that light is able to activate expression of the stem cell inducer WUSCHEL independently of photosynthesis and that this likely involves inter-regional cytokinin signaling. Metabolic signals, on the other hand, are transduced to the meristem through activation of the TARGET OF RAPAMYCIN (TOR) kinase. Surprisingly, TOR is also required for light signal dependent stem cell activation. Thus, the TOR kinase acts as a central integrator of light and metabolic signals and a key regulator of stem cell activation at the shoot apex. PMID:27400267

  5. Pyruvate dehydrogenase complex activity controls metabolic and malignant phenotype in cancer cells.

    PubMed

    McFate, Thomas; Mohyeldin, Ahmed; Lu, Huasheng; Thakar, Jay; Henriques, Jeremy; Halim, Nader D; Wu, Hong; Schell, Michael J; Tsang, Tsz Mon; Teahan, Orla; Zhou, Shaoyu; Califano, Joseph A; Jeoung, Nam Ho; Harris, Robert A; Verma, Ajay

    2008-08-15

    High lactate generation and low glucose oxidation, despite normal oxygen conditions, are commonly seen in cancer cells and tumors. Historically known as the Warburg effect, this altered metabolic phenotype has long been correlated with malignant progression and poor clinical outcome. However, the mechanistic relationship between altered glucose metabolism and malignancy remains poorly understood. Here we show that inhibition of pyruvate dehydrogenase complex (PDC) activity contributes to the Warburg metabolic and malignant phenotype in human head and neck squamous cell carcinoma. PDC inhibition occurs via enhanced expression of pyruvate dehydrogenase kinase-1 (PDK-1), which results in inhibitory phosphorylation of the pyruvate dehydrogenase alpha (PDHalpha) subunit. We also demonstrate that PDC inhibition in cancer cells is associated with normoxic stabilization of the malignancy-promoting transcription factor hypoxia-inducible factor-1alpha (HIF-1alpha) by glycolytic metabolites. Knockdown of PDK-1 via short hairpin RNA lowers PDHalpha phosphorylation, restores PDC activity, reverts the Warburg metabolic phenotype, decreases normoxic HIF-1alpha expression, lowers hypoxic cell survival, decreases invasiveness, and inhibits tumor growth. PDK-1 is an HIF-1-regulated gene, and these data suggest that the buildup of glycolytic metabolites, resulting from high PDK-1 expression, may in turn promote HIF-1 activation, thus sustaining a feed-forward loop for malignant progression. In addition to providing anabolic support for cancer cells, altered fuel metabolism thus supports a malignant phenotype. Correction of metabolic abnormalities offers unique opportunities for cancer treatment and may potentially synergize with other cancer therapies. PMID:18541534

  6. FOXO1 couples metabolic activity and growth state in the vascular endothelium.

    PubMed

    Wilhelm, Kerstin; Happel, Katharina; Eelen, Guy; Schoors, Sandra; Oellerich, Mark F; Lim, Radiance; Zimmermann, Barbara; Aspalter, Irene M; Franco, Claudio A; Boettger, Thomas; Braun, Thomas; Fruttiger, Marcus; Rajewsky, Klaus; Keller, Charles; Brüning, Jens C; Gerhardt, Holger; Carmeliet, Peter; Potente, Michael

    2016-01-14

    Endothelial cells (ECs) are plastic cells that can switch between growth states with different bioenergetic and biosynthetic requirements. Although quiescent in most healthy tissues, ECs divide and migrate rapidly upon proangiogenic stimulation. Adjusting endothelial metabolism to the growth state is central to normal vessel growth and function, yet it is poorly understood at the molecular level. Here we report that the forkhead box O (FOXO) transcription factor FOXO1 is an essential regulator of vascular growth that couples metabolic and proliferative activities in ECs. Endothelial-restricted deletion of FOXO1 in mice induces a profound increase in EC proliferation that interferes with coordinated sprouting, thereby causing hyperplasia and vessel enlargement. Conversely, forced expression of FOXO1 restricts vascular expansion and leads to vessel thinning and hypobranching. We find that FOXO1 acts as a gatekeeper of endothelial quiescence, which decelerates metabolic activity by reducing glycolysis and mitochondrial respiration. Mechanistically, FOXO1 suppresses signalling by MYC (also known as c-MYC), a powerful driver of anabolic metabolism and growth. MYC ablation impairs glycolysis, mitochondrial function and proliferation of ECs while its EC-specific overexpression fuels these processes. Moreover, restoration of MYC signalling in FOXO1-overexpressing endothelium normalizes metabolic activity and branching behaviour. Our findings identify FOXO1 as a critical rheostat of vascular expansion and define the FOXO1-MYC transcriptional network as a novel metabolic checkpoint during endothelial growth and proliferation.

  7. Spore Germination and Carbon Metabolism in Fusarium solani V. Changes in Anaerobic Metabolism and Related Enzyme Activities during Development 1

    PubMed Central

    Cochrane, Vincent W.; Cochrane, Jean C.

    1966-01-01

    Macroconidia of Fusarium solani f. phascoli have no detectable capacity to respire glucose anaerobically; germinated spores and mycelium, on the other hand, ferment glucose, although slowly. Extracts of ungerminated spores contain hexokinase, phosphohexoisomerase, phosphofructokinase, aldolase, triose phosphate dehydrogenase, triose phosphate isomerase, phosphoglyceric kinase, enolase, phosphoglyceric mutase, pyruvate kinase, and pyruvate decarboxylase. It follows, therefore, that the appearance of fermentative capacity during spore germination cannot be ascribed to the de novo synthesis of any of these enzymes. During germination and mycelial development the specific activity of all of the enzymes named except phosphohexoisomerase and aldolase increases 2- to 8-fold. Specific activity of all of the enzymes is substantially higher than the fermentative capacity of intact cells, i.e., none is limiting to anaerobic respiration. The enzymatic assay data are consistent with a conclusion reached earlier on the basis of studies of aerobic glucose metabolism, that the process of germination involves an acceleration of pre-existing metabolic systems rather than an appearance of new pathways. PMID:16656324

  8. Physical Activity Enhances Metabolic Fitness Independently of Cardiorespiratory Fitness in Marathon Runners

    PubMed Central

    Laye, M. J.; Nielsen, M. B.; Hansen, L. S.; Knudsen, T.; Pedersen, B. K.

    2015-01-01

    High levels of cardiovascular fitness (CRF) and physical activity (PA) are associated with decreased mortality and risk to develop metabolic diseases. The independent contributions of CRF and PA to metabolic disease risk factors are unknown. We tested the hypothesis that runners who run consistently >50 km/wk and/or >2 marathons/yr for the last 5 years have superior metabolic fitness compared to matched sedentary subjects (CRF, age, gender, and BMI). Case-control recruitment of 31 pairs of runner-sedentary subjects identified 10 matched pairs with similar VO2max (mL/min/kg) (similar-VO2max). The similar-VO2max group was compared with a group of age, gender, and BMI matched pairs who had the largest difference in VO2max (different-VO2max). Primary outcomes that defined metabolic fitness including insulin response to an oral glucose tolerance test, fasting lipids, and fasting insulin were superior in runners versus sedentary controls despite similar VO2max. Furthermore, performance (velocity at VO2max, running economy), improved exercise metabolism (lactate threshold), and skeletal muscle levels of mitochondrial proteins were superior in runners versus sedentary controls with similar VO2max. In conclusion subjects with a high amount of PA have more positive metabolic health parameters independent of CRF. PA is thus a good marker against metabolic diseases. PMID:25821340

  9. Do sedentary motives adversely affect physical activity? Adding cross-behavioural cognitions to the theory of planned behaviour.

    PubMed

    Rhodes, Ryan E; Blanchard, Chris M

    2008-01-01

    The purpose of this study was to explore whether sedentary behavior cognitions explain physical activity (PA) intention and behavior when integrated within the theory of planned behavior framework (TPB). A random community sample of 206 adults and a sample of 174 undergraduate students completed measures of the TPB pertaining to PA and four popular leisure-time behaviors (TV viewing, computer use, sedentary hobbies, and sedentary socializing) and an adapted Godin Leisure-Time Exercize Questionnaire (community sample = cross-sectional, undergraduate sample = 2-week prospective). Results using ordinary least squares regression provided evidence that TV viewing intention explains additional variance in PA behavior, and affective attitude (community sample) and perceived behavioral control (undergraduate sample) towards TV viewing explains additional variance in PA intention even after controlling for PA-related TPB constructs. These results underscore the potential value of adding sedentary control interventions in concert with PA promotion.

  10. Effect of adding ball-milled achenes to must on bioactive compounds and antioxidant activities in fruit wine.

    PubMed

    Lee, Pao-Ju; Chen, Shaun

    2016-03-01

    This study reports the utilization of ball-milled achenes in fermentation to increase the levels of ellagic acid and total phenol content, as well as to enhance the antioxidant capacity of strawberry wine. Achenes were micronized using ball-milling process, and then added to strawberry must prior to fermentation. The effects of the addition of ball-milled achenes on the ellagic acid and total phenol content in strawberry wine were determined, and the free radical scavenging and iron chelation activities were also analyzed. Quality attributes and acceptance were studied in comparison with a leading commercial strawberry wine for market application. The particle sizes of achenes were reduced from 1.1 mm to 400 nm after 30 min of ball-milling, and this led to an increase in the amount of extracted ellagic acid from 550.72 to 915.24 μg/g. The addition of ball-milled achenes to must led to a 19.72 % and 52.37 % increase in ellagic acid and total phenol content in strawberry wine, respectively. The increase in bioactive compounds resulted in increases of 54.09 %, 51.49 % and 56.97 % in ABTS and DPPH radical scavenging, and ferrous ion chelating activities, respectively. Although the commercial strawberry wine showed greater aroma intensity, no significant differences in overall quality and acceptance among the conventional process, added ball-milled achenes and the leading commercial strawberry wines were found. This study demonstrates that supplementation of ball-milled achenes in fermentation can be beneficial in increasing the levels of bioactive compounds and antioxidative capacity, indicating a good market potential. PMID:27570280

  11. Disturbances to neurotransmitter levels and their metabolic enzyme activity in a freshwater planarian exposed to cadmium.

    PubMed

    Wu, Jui-Pin; Li, Mei-Hui; Chen, Jhih-Sheng; Chung, Szu-Yao; Lee, Hui-Ling

    2015-03-01

    Using specific neurobehaviors as endpoints, previous studies suggested that planarian neurotransmission systems could be targets of Cd neurotoxicity. However, direct evidence for disturbed neurotransmission systems by Cd in treated planarians is still lacking. In planarians, dopamine (DA) and serotonin (5-HT) play critical roles in neuromuscular function, but little is known about their metabolic degradation. Therefore, in this study, we attempted to determine the appearances of DA, 5-HT, and their metabolic products in the freshwater planarian Dugesia japonica, characterize the activity of enzymes involved in their metabolism, and investigate the effects of Cd on planarian 5-HTergic and DAergic neurotransmission systems. Only DA, 5-HT, and 5-hydroxyindole-3-acetic acid (5-HIAA) were found in planarian tissues. Further enzymatic study revealed the activity of planarian monoamine oxidase (MAO) but not catechol-O-methyl transferase (COMT). These findings suggest that planarian MAO catalyzes the metabolism of 5-HT into 5-HIAA. However, DA metabolites from the MAO-involved metabolic pathway were not found, which might be due to a lack of COMT activity. Finally, in Cd-treated planarians, tissue levels of 5-HT and DA were decreased and MAO activity altered, suggesting that planarian neurotransmission systems are disturbed following Cd treatment.

  12. How Effective Are Active Videogames Among the Young and the Old? Adding Meta-analyses to Two Recent Systematic Reviews

    PubMed Central

    Crutzen, Rik; Lu, Amy Shirong

    2014-01-01

    Abstract Objective: Two recent systematic reviews have surveyed the existing evidence for the effectiveness of active videogames in children/adolescents and in elderly people. In the present study, effect sizes were added to these systematic reviews, and meta-analyses were performed. Materials and Methods: All reviewed studies were considered for inclusion in the meta-analyses, but only studies were included that investigated the effectiveness of active videogames, used an experimental design, and used actual health outcomes as the outcome measures (body mass index for children/adolescents [k=5] and functional balance for the elderly [k=6]). Results: The average effect of active videogames in children and adolescents was small and nonsignificant: Hedges' g=0.20 (95 percent confidence interval, −0.08 to 0.48). Limited heterogeneity was observed, and no moderator analyses were performed. For the effect of active videogames on functional balance in the elderly, the analyses revealed a medium-sized and significant effect of g=0.68 (95 percent confidence interval, 0.13–1.24). For the elderly studies, substantial heterogeneity was observed. Moderator analyses showed that there were no significant effects of using a no-treatment control group versus an alternative treatment control group or of using games that were especially created for health-promotion purposes versus off-the-shelf games. Also, intervention duration and frequency, sample size, study quality, and dropout did not significantly moderate the effect of active videogames. Conclusions: The results of these meta-analyses provide preliminary evidence that active videogames can have positive effects on relevant outcome measures in children/adolescents and elderly individuals. PMID:26192486

  13. c-Myc activates multiple metabolic networks to generate substrates for cell-cycle entry.

    PubMed

    Morrish, F; Isern, N; Sadilek, M; Jeffrey, M; Hockenbery, D M

    2009-07-01

    Cell proliferation requires the coordinated activity of cytosolic and mitochondrial metabolic pathways to provide ATP and building blocks for DNA, RNA and protein synthesis. Many metabolic pathway genes are targets of the c-myc oncogene and cell-cycle regulator. However, the contribution of c-Myc to the activation of cytosolic and mitochondrial metabolic networks during cell-cycle entry is unknown. Here, we report the metabolic fates of [U-(13)C] glucose in serum-stimulated myc(-/-) and myc(+/+) fibroblasts by (13)C isotopomer NMR analysis. We demonstrate that endogenous c-myc increased (13)C labeling of ribose sugars, purines and amino acids, indicating partitioning of glucose carbons into C1/folate and pentose phosphate pathways, and increased tricarboxylic acid cycle turnover at the expense of anaplerotic flux. Myc expression also increased global O-linked N-acetylglucosamine protein modification, and inhibition of hexosamine biosynthesis selectively reduced growth of Myc-expressing cells, suggesting its importance in Myc-induced proliferation. These data reveal a central organizing function for the Myc oncogene in the metabolism of cycling cells. The pervasive deregulation of this oncogene in human cancers may be explained by its function in directing metabolic networks required for cell proliferation.

  14. c-Myc activates multiple metabolic networks to generate substrates for cell-cycle entry.

    SciTech Connect

    Morrish, Fionnuala M.; Isern, Nancy; Sadilek, Martin; Jeffrey, Mark; Hockenbery, David M.

    2009-05-18

    Cell proliferation requires the coordinated activity of cytosolic and mitochondrial metabolic pathways to provide ATP and building blocks for DNA, RNA, and protein synthesis. Many metabolic pathway genes are targets of the c-myc oncogene and cell cycle regulator. However, the contribution of c-Myc to the activation of cytosolic and mitochondrial metabolic networks during cell cycle entry is unknown. Here, we report the metabolic fates of [U-13C] glucose in serum-stimulated myc-/- and myc+/+ fibroblasts by 13C isotopomer NMR analysis. We demonstrate that endogenous c-myc increased 13C-labeling of ribose sugars, purines, and amino acids, indicating partitioning of glucose carbons into C1/folate and pentose phosphate pathways, and increased tricarboxylic acid cycle turnover at the expense of anaplerotic flux. Myc expression also increased global O-linked GlcNAc protein modification, and inhibition of hexosamine biosynthesis selectively reduced growth of Myc-expressing cells, suggesting its importance in Myc-induced proliferation. These data reveal a central organizing role for the Myc oncogene in the metabolism of cycling cells. The pervasive deregulation of this oncogene in human cancers may be explained by its role in directing metabolic networks required for cell proliferation.

  15. Brown Adipose Tissue Activation Is Linked to Distinct Systemic Effects on Lipid Metabolism in Humans.

    PubMed

    Chondronikola, Maria; Volpi, Elena; Børsheim, Elisabet; Porter, Craig; Saraf, Manish K; Annamalai, Palam; Yfanti, Christina; Chao, Tony; Wong, Daniel; Shinoda, Kosaku; Labbė, Sebastien M; Hurren, Nicholas M; Cesani, Fernardo; Kajimura, Shingo; Sidossis, Labros S

    2016-06-14

    Recent studies suggest that brown adipose tissue (BAT) plays a role in energy and glucose metabolism in humans. However, the physiological significance of human BAT in lipid metabolism remains unknown. We studied 16 overweight/obese men during prolonged, non-shivering cold and thermoneutral conditions using stable isotopic tracer methodologies in conjunction with hyperinsulinemic-euglycemic clamps and BAT and white adipose tissue (WAT) biopsies. BAT volume was significantly associated with increased whole-body lipolysis, triglyceride-free fatty acid (FFA) cycling, FFA oxidation, and adipose tissue insulin sensitivity. Functional analysis of BAT and WAT demonstrated the greater thermogenic capacity of BAT compared to WAT, while molecular analysis revealed a cold-induced upregulation of genes involved in lipid metabolism only in BAT. The accelerated mobilization and oxidation of lipids upon BAT activation supports a putative role for BAT in the regulation of lipid metabolism in humans. PMID:27238638

  16. Role of N-methylolpentamethylmelamine in the metabolic activation of hexamethylmelamine

    SciTech Connect

    Ames, M.M.; Sanders, M.E.; Tiede, W.S.

    1983-02-01

    Hexamethylmelamine (HMM) is metabolized by rat hepatic microsomal preparations to reactive species which covalently bind to microsomal protein and to calf thymus DNA added to microsomal incubation mixtures. Covalent binding to macromolecules is dependent on the presence of molecular oxygen and reduced nicotinamide adenine dinucleotide phosphate and is catalyzed by cytochrome P-450 monooxygenases. Reduced nicotinamide adenine dinucleotide-dependent covalent binding of (methyl-/sup 14/C)HMM to microsomal protein is greater than that of (ring-/sup 14/C)HMM. Reduced nicotinamide adenine dinucleotide phosphate-dependent covalent binding of (ring-/sup 14/C)HMM and (methyl-/sup 14/C)HMM to calf thymus DNA added to microsomal incubation mixtures are approximately equal. The (ring-/sup 14/C)-labeled carbinolamine intermediate in HMM demethylation, N-methylolpentamethylmelamine, covalently binds to microsomal protein and, to a much greater extent, to calf thymus DNA.

  17. Specific activity effect in the metabolism of Tc

    SciTech Connect

    Ennis, M.E. Jr.; Johnson, J.E.; Ward, G.M.; Voigt, G.M.

    1988-02-01

    A study of transfer to milk of three isotopes of Tc indicated different results for /sup 99m/TcO/sub 4/-, /sup 95m/TcO/sub 4/-, and /sup 99/TcO/sub 4/-. When the three isotopes were given orally to lactating goats in separate experiments, the milk transfer coefficients increased with decreasing specific activity. Gut absorption of Tc administered as pertechnetate (TcO/sub 4/-) was decreased by reduction of TcO/sub 4/- in the rumen. The rate of reduction of TcO/sub 4/- in the rumen was greater for higher specific activity doses of Tc. These results suggest that the specific activity of a radioisotope may significantly influence the estimated dose to humans from contaminated milk and, probably, other food products.

  18. TRPV1 activation improves exercise endurance and energy metabolism through PGC-1α upregulation in mice.

    PubMed

    Luo, Zhidan; Ma, Liqun; Zhao, Zhigang; He, Hongbo; Yang, Dachun; Feng, Xiaoli; Ma, Shuangtao; Chen, Xiaoping; Zhu, Tianqi; Cao, Tingbing; Liu, Daoyan; Nilius, Bernd; Huang, Yu; Yan, Zhencheng; Zhu, Zhiming

    2012-03-01

    Impaired aerobic exercise capacity and skeletal muscle dysfunction are associated with cardiometabolic diseases. Acute administration of capsaicin enhances exercise endurance in rodents, but the long-term effect of dietary capsaicin is unknown. The capsaicin receptor, the transient receptor potential vanilloid 1 (TRPV1) cation channel has been detected in skeletal muscle, the role of which remains unclear. Here we report the function of TRPV1 in cultured C2C12 myocytes and the effect of TRPV1 activation by dietary capsaicin on energy metabolism and exercise endurance of skeletal muscles in mice. In vitro, capsaicin increased cytosolic free calcium and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) expression in C2C12 myotubes through activating TRPV1. In vivo, PGC-1α in skeletal muscle was upregulated by capsaicin-induced TRPV1 activation or genetic overexpression of TRPV1 in mice. TRPV1 activation increased the expression of genes involved in fatty acid oxidation and mitochondrial respiration, promoted mitochondrial biogenesis, increased oxidative fibers, enhanced exercise endurance and prevented high-fat diet-induced metabolic disorders. Importantly, these effects of capsaicin were absent in TRPV1-deficient mice. We conclude that TRPV1 activation by dietary capsaicin improves energy metabolism and exercise endurance by upregulating PGC-1α in skeletal muscles. The present results indicate a novel therapeutic strategy for managing metabolic diseases and improving exercise endurance.

  19. Understanding Fatty Acid Metabolism through an Active Learning Approach

    ERIC Educational Resources Information Center

    Fardilha, M.; Schrader, M.; da Cruz e Silva, O. A. B.; da Cruz e Silva, E. F.

    2010-01-01

    A multi-method active learning approach (MALA) was implemented in the Medical Biochemistry teaching unit of the Biomedical Sciences degree at the University of Aveiro, using problem-based learning as the main learning approach. In this type of learning strategy, students are involved beyond the mere exercise of being taught by listening. Less…

  20. Systems biology network-based discovery of a small molecule activator BL-AD008 targeting AMPK/ZIPK and inducing apoptosis in cervical cancer

    PubMed Central

    Tong, Xupeng; Zhang, Jin; Zhang, Yonghui; Ouyang, Liang; Liu, Bo; Huang, Jian

    2015-01-01

    The aim of this study was to discover a small molecule activator BL-AD008 targeting AMPK/ZIPK and inducing apoptosis in cervical cancer. In this study, we systematically constructed the global protein-protein interaction (PPI) network and predicted apoptosis-related protein connections by the Naïve Bayesian model. Then, we identified some classical apoptotic PPIs and other previously unrecognized PPIs between apoptotic kinases, such as AMPK and ZIPK. Subsequently, we screened a series of candidate compounds targeting AMPK/ZIPK, synthesized some compounds and eventually discovered a novel dual-target activator (BL-AD008). Moreover, we found BL-AD008 bear remarkable anti-proliferative activities toward cervical cancer cells and could induce apoptosis by death-receptor and mitochondrial pathways. Additionally, we found that BL-AD008-induced apoptosis was affected by the combination of AMPK and ZIPK. Then, we found that BL-AD008 bear its anti-tumor activities and induced apoptosis by targeting AMPK/ZIPK in vivo. In conclusion, these results demonstrate the ability of systems biology network to identify some key apoptotic kinase targets AMPK and ZIPK; thus providing a dual-target small molecule activator (BL-AD008) as a potential new apoptosis-modulating drug in future cervical cancer therapy. PMID:25797270

  1. The roles of peroxisome proliferator-activated receptors in the metabolic syndrome.

    PubMed

    Mansour, Mahmoud

    2014-01-01

    The epidemic of obesity and its association with insulin resistance, glucose intolerance, hypertension, and dyslipidemia, collectively known as the metabolic syndrome or syndrome X, is one of the most challenging health problems facing industrialized countries. The nuclear receptors, peroxisome proliferator-activated receptors (PPARs alpha (α), beta (β) also known as delta (δ), and gamma (γ)), have well-documented roles in lipid and glucose metabolism. Pharmacologically, PPARα is activated by fibrate hypolipidemic drugs, whereas PPARγ is activated by insulin sensitizers thiazolidinediones (TZDs). No marketed drug is yet available for PPARβ(δ). The identification of fibrates and TZDs as respective ligands for PPARα and PPARγ was a groundbreaking finding that sparked notable pharmaceutical interest in PPARs as potential drug targets for treatment of the metabolic syndrome. Limiting side effects associated with clinical use of TZDs have emerged in recent years. New and novel PPAR drugs with broad safety margins and therapeutic potentials for the metabolic syndrome are in development. These include partial, dual, or pan PPAR agonists; PPAR antagonists; and selective PPAR modulators. The objective of this chapter is to highlight the therapeutic benefits of targeting more than one PPAR subtype in the treatment of the metabolic syndrome. The pros and cons observed during clinical use of TZDs and the strategies and progress made in the production of new generations of safe and effective PPAR ligands are discussed. PMID:24373239

  2. Diminished leptin signaling can alter circadian rhythm of metabolic activity and feeding.

    PubMed

    Hsuchou, Hung; Wang, Yuping; Cornelissen-Guillaume, Germaine G; Kastin, Abba J; Jang, Eunjin; Halberg, Franz; Pan, Weihong

    2013-10-01

    Leptin, a hormone mainly produced by fat cells, shows cell-specific effects to regulate feeding and metabolic activities. We propose that an important feature of metabolic dysregulation resulting in obesity is the loss of the circadian rhythm of biopotentials. This was tested in the pan-leptin receptor knockout (POKO) mice newly generated in our laboratory. In the POKO mice, leptin no longer induced pSTAT-3 signaling after intracerebroventricular injection. Three basic phenotypes were observed: the heterozygotes had similar weight and adiposity as the wild-type (WT) mice (>60% of the mice); the homozygotes were either fatter (∼30%), or rarely leaner (<5%) than the WT mice. By early adulthood, the POKO mice had higher average body weight and adiposity than their respective same-sex WT littermate controls, and this was consistent among different batches. The homozygote fat POKO showed significant reduction of midline estimating statistic of rhythm of circadian parameters, and shifts of ultradian rhythms. The blunted circadian rhythm of these extremely obese POKO mice was also seen in their physical inactivity, longer feeding bouts, and higher food intake. The extent of obesity correlated with the blunted circadian amplitude, accumulative metabolic and locomotor activities, and the severity of hyperphagia. This contrasts with the heterozygote POKO mice which showed little obesity and metabolic disturbance, and only subtle changes of the circadian rhythm of metabolic activity without alterations in feeding behavior. The results provide a novel aspect of leptin resistance, almost manifesting as an "all or none" phenomenon.

  3. Metabolic activity of sperm cells: correlation with sperm cell concentration, viability and motility in the rabbit.

    PubMed

    Sabés-Alsina, Maria; Planell, Núria; Gil, Sílvia; Tallo-Parra, Oriol; Maya-Soriano, Maria José; Taberner, Ester; Piles, Miriam; Sabés, Manel; Lopez-Bejar, Manel

    2016-10-01

    The resazurin reduction test (RRT) is a useful technique to assess the metabolic rate of sperm cells. RRT depends on the ability of metabolically active cells to reduce the non-fluorescent dye resazurin to the fluorescent resorufin. The aim of this study was to develop a vital fluorometric method to evaluate metabolic activity of rabbit sperm cells. Twenty-five rabbit males were included in the study. Viability and morphology, motility and metabolic activity were evaluated using an eosin-nigrosin staining, a computer-assisted semen analysis (CASA) and the RRT, respectively. Spearman rank correlation analysis was used to determine the correlation between RRT and semen parameters. After evaluation, a concentration of 10 × 106 sperm cells/ml was selected for further experiments with RRT. No significant correlation was found between the RRT results and the motility parameters. However, after RRT a significant positive correlation between relative fluorescence units and the percentage of alive spermatozoa (r = 0.62; P = 0.001) and a negative one with the percentage of sperm cells with acrosomic abnormalities (r = -0.45; P < 0.05) were detected. The vital assessment of metabolic rate of sperm cells by RRT could provide more information about semen quality than other routine semen analysis, correlating with sperm viability and acrosome status information.

  4. Mechanisms and metabolic regulation of PPARα activation in Nile tilapia (Oreochromis niloticus).

    PubMed

    Ning, Li-Jun; He, An-Yuan; Li, Jia-Min; Lu, Dong-Liang; Jiao, Jian-Gang; Li, Ling-Yu; Li, Dong-Liang; Zhang, Mei-Ling; Chen, Li-Qiao; Du, Zhen-Yu

    2016-09-01

    Although the key metabolic regulatory functions of mammalian peroxisome proliferator-activated receptor α (PPARα) have been thoroughly studied, the molecular mechanisms and metabolic regulation of PPARα activation in fish are less known. In the first part of the present study, Nile tilapia (Nt)PPARα was cloned and identified, and high mRNA expression levels were detected in the brain, liver, and heart. NtPPARα was activated by an agonist (fenofibrate) and by fasting and was verified in primary hepatocytes and living fish by decreased phosphorylation of NtPPARα and/or increased NtPPARα mRNA and protein expression. In the second part of the present work, fenofibrate was fed to fish or fish were fasted for 4weeks to investigate the metabolic regulatory effects of NtPPARα. A transcriptomic study was also performed. The results indicated that fenofibrate decreased hepatic triglyceride and 18C-series fatty acid contents but increased the catabolic rate of intraperitoneally injected [1-(14)C] palmitate in vivo, hepatic mitochondrial β-oxidation efficiency, the quantity of cytochrome b DNA, and carnitine palmitoyltransferase-1a mRNA expression. Fenofibrate also increased serum glucose, insulin, and lactate concentrations. Fasting had stronger hypolipidemic and gene regulatory effects than those of fenofibrate. Taken together, we conclude that: 1) liver is one of the main target tissues of the metabolic regulation of NtPPARα activation; 2) dephosphorylation is the basal NtPPARα activation mechanism rather than enhanced mRNA and protein expression; 3) activated NtPPARα has a hypolipidemic effect by increasing activity and the number of hepatic mitochondria; and 4) PPARα activation affects carbohydrate metabolism by altering energy homeostasis among nutrients. PMID:27320014

  5. Active Smoking and Risk of Metabolic Syndrome: A Meta-Analysis of Prospective Studies

    PubMed Central

    Ning, Guang

    2012-01-01

    Background Epidemiological evidence suggests that smoking has been associated with emergence of metabolic syndrome. However, data on this issue are inconsistent and controversial. We therefore conducted a meta-analysis to examine the association between smoking and metabolic syndrome. Methodology and Principal Findings We searched the Medline, Embase and the Cochrane Library database up to March 2012 to identify prospective cohort studies related to smoking and metabolic syndrome. Reference lists of retrieved articles were also reviewed. Summary effect estimates were derived using a random-effects model and stratified by gender, smoking dose, follow-up duration and geographical area. Primary analysis of 13 studies involving 56,691 participants and 8,688 cases detected a significant positive association between active smoking and risk of metabolic syndrome (pooled relative risk [RR] 1.26, 95% CI: 1.10–1.44). Estimates of effects were substantially consistent in the stratified analyses. In the dose-response analysis, risk of metabolic syndrome was stronger for active male smokers (pooled RR 1.34, 95% CI: 1.20–1.50) than it was for former male smokers (pooled RR 1.19, 95% CI: 1.00–1.42), and greater for heavy smokers (pooled RR 1.42, 95% CI: 1.27–1.59) compared with light smokers (pooled RR 1.10, 95% CI: 0.90–1.35). No evidence of statistical publication bias was found (Egger' s test P = 0.227, Begg' s test P = 0.113). Conclusions Active smoking is associated with development of metabolic syndrome. Smoking cessation appears to reduce the risk of metabolic syndrome. PMID:23082217

  6. CREB and the CRTC co-activators: sensors for hormonal and metabolic signals.

    PubMed

    Altarejos, Judith Y; Montminy, Marc

    2011-03-01

    The cyclic AMP-responsive element-binding protein (CREB) is phosphorylated in response to a wide variety of signals, yet target gene transcription is only increased in a subset of cases. Recent studies indicate that CREB functions in concert with a family of latent cytoplasmic co-activators called cAMP-regulated transcriptional co-activators (CRTCs), which are activated through dephosphorylation. A dual requirement for CREB phosphorylation and CRTC dephosphorylation is likely to explain how these activator-co-activator cognates discriminate between different stimuli. Following their activation, CREB and CRTCs mediate the effects of fasting and feeding signals on the expression of metabolic programmes in insulin-sensitive tissues.

  7. Metabolic Features of Protochlamydia amoebophila Elementary Bodies – A Link between Activity and Infectivity in Chlamydiae

    PubMed Central

    Watzka, Margarete; Wultsch, Anna; Tziotis, Dimitrios; Montanaro, Jacqueline; Richter, Andreas; Schmitt-Kopplin, Philippe; Horn, Matthias

    2013-01-01

    The Chlamydiae are a highly successful group of obligate intracellular bacteria, whose members are remarkably diverse, ranging from major pathogens of humans and animals to symbionts of ubiquitous protozoa. While their infective developmental stage, the elementary body (EB), has long been accepted to be completely metabolically inert, it has recently been shown to sustain some activities, including uptake of amino acids and protein biosynthesis. In the current study, we performed an in-depth characterization of the metabolic capabilities of EBs of the amoeba symbiont Protochlamydia amoebophila. A combined metabolomics approach, including fluorescence microscopy-based assays, isotope-ratio mass spectrometry (IRMS), ion cyclotron resonance Fourier transform mass spectrometry (ICR/FT-MS), and ultra-performance liquid chromatography mass spectrometry (UPLC-MS) was conducted, with a particular focus on the central carbon metabolism. In addition, the effect of nutrient deprivation on chlamydial infectivity was analyzed. Our investigations revealed that host-free P. amoebophila EBs maintain respiratory activity and metabolize D-glucose, including substrate uptake as well as host-free synthesis of labeled metabolites and release of labeled CO2 from 13C-labeled D-glucose. The pentose phosphate pathway was identified as major route of D-glucose catabolism and host-independent activity of the tricarboxylic acid (TCA) cycle was observed. Our data strongly suggest anabolic reactions in P. amoebophila EBs and demonstrate that under the applied conditions D-glucose availability is essential to sustain metabolic activity. Replacement of this substrate by L-glucose, a non-metabolizable sugar, led to a rapid decline in the number of infectious particles. Likewise, infectivity of Chlamydia trachomatis, a major human pathogen, also declined more rapidly in the absence of nutrients. Collectively, these findings demonstrate that D-glucose is utilized by P. amoebophila EBs and provide

  8. Flexibility in Anaerobic Metabolism as Revealed in a Mutant of Chlamydomonas reinhardtii Lacking Hydrogenase Activity

    SciTech Connect

    Dubini, A.; Mus, F.; Seibert, M.; Grossman, A. R.; Posewitz, M. C.

    2009-03-13

    The green alga Chlamydomonas reinhardtii has a network of fermentation pathways that become active when cells acclimate to anoxia. Hydrogenase activity is an important component of this metabolism, and we have compared metabolic and regulatory responses that accompany anaerobiosis in wild-type C. reinhardtii cells and a null mutant strain for the HYDEF gene (hydEF-1 mutant), which encodes an [FeFe] hydrogenase maturation protein. This mutant has no hydrogenase activity and exhibits elevated accumulation of succinate and diminished production of CO2 relative to the parental strain during dark, anaerobic metabolism. In the absence of hydrogenase activity, increased succinate accumulation suggests that the cells activate alternative pathways for pyruvate metabolism, which contribute to NAD(P)H reoxidation, and continued glycolysis and fermentation in the absence of O2. Fermentative succinate production potentially proceeds via the formation of malate, and increases in the abundance of mRNAs encoding two malateforming enzymes, pyruvate carboxylase and malic enzyme, are observed in the mutant relative to the parental strain following transfer of cells from oxic to anoxic conditions. Although C. reinhardtii has a single gene encoding pyruvate carboxylase, it has six genes encoding putative malic enzymes. Only one of the malic enzyme genes, MME4, shows a dramatic increase in expression (mRNA abundance) in the hydEF-1 mutant during anaerobiosis. Furthermore, there are marked increases in transcripts encoding fumarase and fumarate reductase, enzymes putatively required to convert malate to succinate. These results illustrate the marked metabolic flexibility of C. reinhardtii and contribute to the development of an informed model of anaerobic metabolism in this and potentially other algae.

  9. Metabolic features of Protochlamydia amoebophila elementary bodies--a link between activity and infectivity in Chlamydiae.

    PubMed

    Sixt, Barbara S; Siegl, Alexander; Müller, Constanze; Watzka, Margarete; Wultsch, Anna; Tziotis, Dimitrios; Montanaro, Jacqueline; Richter, Andreas; Schmitt-Kopplin, Philippe; Horn, Matthias

    2013-01-01

    The Chlamydiae are a highly successful group of obligate intracellular bacteria, whose members are remarkably diverse, ranging from major pathogens of humans and animals to symbionts of ubiquitous protozoa. While their infective developmental stage, the elementary body (EB), has long been accepted to be completely metabolically inert, it has recently been shown to sustain some activities, including uptake of amino acids and protein biosynthesis. In the current study, we performed an in-depth characterization of the metabolic capabilities of EBs of the amoeba symbiont Protochlamydia amoebophila. A combined metabolomics approach, including fluorescence microscopy-based assays, isotope-ratio mass spectrometry (IRMS), ion cyclotron resonance Fourier transform mass spectrometry (ICR/FT-MS), and ultra-performance liquid chromatography mass spectrometry (UPLC-MS) was conducted, with a particular focus on the central carbon metabolism. In addition, the effect of nutrient deprivation on chlamydial infectivity was analyzed. Our investigations revealed that host-free P. amoebophila EBs maintain respiratory activity and metabolize D-glucose, including substrate uptake as well as host-free synthesis of labeled metabolites and release of labeled CO2 from (13)C-labeled D-glucose. The pentose phosphate pathway was identified as major route of D-glucose catabolism and host-independent activity of the tricarboxylic acid (TCA) cycle was observed. Our data strongly suggest anabolic reactions in P. amoebophila EBs and demonstrate that under the applied conditions D-glucose availability is essential to sustain metabolic activity. Replacement of this substrate by L-glucose, a non-metabolizable sugar, led to a rapid decline in the number of infectious particles. Likewise, infectivity of Chlamydia trachomatis, a major human pathogen, also declined more rapidly in the absence of nutrients. Collectively, these findings demonstrate that D-glucose is utilized by P. amoebophila EBs and provide

  10. Biological Activity of Vegetal Extracts Containing Phenols on Plant Metabolism.

    PubMed

    Ertani, Andrea; Pizzeghello, Diego; Francioso, Ornella; Tinti, Anna; Nardi, Serenella

    2016-01-01

    The influence of vegetal extracts derived from red grape, blueberry fruits and hawthorn leaves on Zea mays L. plant growth and the activity of phenylalanine ammonia-lyase (PAL), a key enzyme of the phenylpropanoid pathway, was investigated in laboratory experiments. The extracts were characterized using FT-IR and Raman spectroscopies in order to obtain a pattern of the main functional groups. In addition, phenols content was determined by HPLC, whereas the content of indoleacetic acid and isopentenyladenosine hormones was determined by ELISA test and the auxin and gibberellin-like activities by plant-bioassays. The treated maize revealed increased root and leaf biomass, chlorophyll and sugars content with respect to untreated plants. Hawthorn, red grape skin and blueberry at 1.0 mL/L induced high p-coumaric content values, whilst hawthorn also showed high amounts of gallic and p-hydroxybenzoic acids. PAL activity induced by hawthorn at 1.0 mL/L had the highest values (11.1-fold UNT) and was strongly and linearly related with the sum of leaf phenols. Our results suggest that these vegetal extracts contain more than one group of plant-promoting substances. PMID:26867189

  11. Biological Activity of Vegetal Extracts Containing Phenols on Plant Metabolism.

    PubMed

    Ertani, Andrea; Pizzeghello, Diego; Francioso, Ornella; Tinti, Anna; Nardi, Serenella

    2016-02-08

    The influence of vegetal extracts derived from red grape, blueberry fruits and hawthorn leaves on Zea mays L. plant growth and the activity of phenylalanine ammonia-lyase (PAL), a key enzyme of the phenylpropanoid pathway, was investigated in laboratory experiments. The extracts were characterized using FT-IR and Raman spectroscopies in order to obtain a pattern of the main functional groups. In addition, phenols content was determined by HPLC, whereas the content of indoleacetic acid and isopentenyladenosine hormones was determined by ELISA test and the auxin and gibberellin-like activities by plant-bioassays. The treated maize revealed increased root and leaf biomass, chlorophyll and sugars content with respect to untreated plants. Hawthorn, red grape skin and blueberry at 1.0 mL/L induced high p-coumaric content values, whilst hawthorn also showed high amounts of gallic and p-hydroxybenzoic acids. PAL activity induced by hawthorn at 1.0 mL/L had the highest values (11.1-fold UNT) and was strongly and linearly related with the sum of leaf phenols. Our results suggest that these vegetal extracts contain more than one group of plant-promoting substances.

  12. Timing and Variability of Galactose Metabolic Gene Activation Depend on the Rate of Environmental Change

    PubMed Central

    Ma, Bo; Ott, William; Josić, Krešimir; Bennett, Matthew R.

    2015-01-01

    Modulation of gene network activity allows cells to respond to changes in environmental conditions. For example, the galactose utilization network in Saccharomyces cerevisiae is activated by the presence of galactose but repressed by glucose. If both sugars are present, the yeast will first metabolize glucose, depleting it from the extracellular environment. Upon depletion of glucose, the genes encoding galactose metabolic proteins will activate. Here, we show that the rate at which glucose levels are depleted determines the timing and variability of galactose gene activation. Paradoxically, we find that Gal1p, an enzyme needed for galactose metabolism, accumulates more quickly if glucose is depleted slowly rather than taken away quickly. Furthermore, the variability of induction times in individual cells depends non-monotonically on the rate of glucose depletion and exhibits a minimum at intermediate depletion rates. Our mathematical modeling suggests that the dynamics of the metabolic transition from glucose to galactose are responsible for the variability in galactose gene activation. These findings demonstrate that environmental dynamics can determine the phenotypic outcome at both the single-cell and population levels. PMID:26200924

  13. Enrichment of specific electro-active microorganisms and enhancement of methane production by adding granular activated carbon in anaerobic reactors.

    PubMed

    Lee, Jung-Yeol; Lee, Sang-Hoon; Park, Hee-Deung

    2016-04-01

    Direct interspecies electron transfer (DIET) via conductive materials can provide significant benefits to anaerobic methane formation in terms of production amount and rate. Although granular activated carbon (GAC) demonstrated its applicability in facilitating DIET in methanogenesis, DIET in continuous flow anaerobic reactors has not been verified. Here, evidences of DIET via GAC were explored. The reactor supplemented with GAC showed 1.8-fold higher methane production rate than that without GAC (35.7 versus 20.1±7.1mL-CH4/d). Around 34% of methane formation was attributed to the biomass attached to GAC. Pyrosequencing of 16S rRNA gene demonstrated the enrichment of exoelectrogens (e.g. Geobacter) and hydrogenotrophic methanogens (e.g. Methanospirillum and Methanolinea) from the biomass attached to GAC. Furthermore, anodic and cathodic currents generation was observed in an electrochemical cell containing GAC biomass. Taken together, GAC supplementation created an environment for enriching the microorganisms involved in DIET, which increased the methane production rate. PMID:26836607

  14. Metabolic pathways and activity-dependent modulation of glutamate concentration in the human brain.

    PubMed

    Mangia, Silvia; Giove, Federico; Dinuzzo, Mauro

    2012-11-01

    Glutamate is one of the most versatile molecules present in the human brain, involved in protein synthesis, energy production, ammonia detoxification, and transport of reducing equivalents. Aside from these critical metabolic roles, glutamate plays a major part in brain function, being not only the most abundant excitatory neurotransmitter, but also the precursor for γ-aminobutyric acid, the predominant inhibitory neurotransmitter. Regulation of glutamate levels is pivotal for normal brain function, as abnormal extracellular concentration of glutamate can lead to impaired neurotransmission, neurodegeneration and even neuronal death. Understanding how the neuron-astrocyte functional and metabolic interactions modulate glutamate concentration during different activation status and under physiological and pathological conditions is a challenging task, and can only be tentatively estimated from current literature. In this paper, we focus on describing the various metabolic pathways which potentially affect glutamate concentration in the brain, and emphasize which ones are likely to produce the variations in glutamate concentration observed during enhanced neuronal activity in human studies.

  15. A novel activity of microsomal epoxide hydrolase: metabolism of the endocannabinoid 2-arachidonoylglycerol

    PubMed Central

    Nithipatikom, Kasem; Endsley, Michael P.; Pfeiffer, Adam W.; Falck, John R.; Campbell, William B.

    2014-01-01

    Microsomal epoxide hydrolase (EPHX1, EC 3.3.2.9) is a highly abundant α/β-hydrolase enzyme that is known for its catalytical epoxide hydrolase activity. A wide range of EPHX1 functions have been demonstrated including xenobiotic metabolism; however, characterization of its endogenous substrates is limited. In this study, we present evidence that EPHX1 metabolizes the abundant endocannabinoid 2-arachidonoylglycerol (2-AG) to free arachidonic acid (AA) and glycerol. The EPHX1 metabolism of 2-AG was demonstrated using commercially available EPHX1 microsomes as well as PC-3 cells overexpressing EPHX1. Conversely, EPHX1 siRNA markedly reduced the EPHX1 expression and 2-AG metabolism in HepG2 cells and LNCaP cells. A selective EPHX1 inhibitor, 10-hydroxystearamide, inhibited 2-AG metabolism and hydrolysis of a well-known EPHX1 substrate, cis-stilbene oxide. Among the inhibitors studied, a serine hydrolase inhibitor, methoxy-arachidonyl fluorophosphate, was the most potent inhibitor of 2-AG metabolism by EPHX1 microsomes. These results demonstrate that 2-AG is an endogenous substrate for EPHX1, a potential role of EPHX1 in the endocannabinoid signaling and a new AA biosynthetic pathway. PMID:24958911

  16. Constrained Total Energy Expenditure and Metabolic Adaptation to Physical Activity in Adult Humans.

    PubMed

    Pontzer, Herman; Durazo-Arvizu, Ramon; Dugas, Lara R; Plange-Rhule, Jacob; Bovet, Pascal; Forrester, Terrence E; Lambert, Estelle V; Cooper, Richard S; Schoeller, Dale A; Luke, Amy

    2016-02-01

    Current obesity prevention strategies recommend increasing daily physical activity, assuming that increased activity will lead to corresponding increases in total energy expenditure and prevent or reverse energy imbalance and weight gain [1-3]. Such Additive total energy expenditure models are supported by exercise intervention and accelerometry studies reporting positive correlations between physical activity and total energy expenditure [4] but are challenged by ecological studies in humans and other species showing that more active populations do not have higher total energy expenditure [5-8]. Here we tested a Constrained total energy expenditure model, in which total energy expenditure increases with physical activity at low activity levels but plateaus at higher activity levels as the body adapts to maintain total energy expenditure within a narrow range. We compared total energy expenditure, measured using doubly labeled water, against physical activity, measured using accelerometry, for a large (n = 332) sample of adults living in five populations [9]. After adjusting for body size and composition, total energy expenditure was positively correlated with physical activity, but the relationship was markedly stronger over the lower range of physical activity. For subjects in the upper range of physical activity, total energy expenditure plateaued, supporting a Constrained total energy expenditure model. Body fat percentage and activity intensity appear to modulate the metabolic response to physical activity. Models of energy balance employed in public health [1-3] should be revised to better reflect the constrained nature of total energy expenditure and the complex effects of physical activity on metabolic physiology.

  17. Constrained Total Energy Expenditure and Metabolic Adaptation to Physical Activity in Adult Humans.

    PubMed

    Pontzer, Herman; Durazo-Arvizu, Ramon; Dugas, Lara R; Plange-Rhule, Jacob; Bovet, Pascal; Forrester, Terrence E; Lambert, Estelle V; Cooper, Richard S; Schoeller, Dale A; Luke, Amy

    2016-02-01

    Current obesity prevention strategies recommend increasing daily physical activity, assuming that increased activity will lead to corresponding increases in total energy expenditure and prevent or reverse energy imbalance and weight gain [1-3]. Such Additive total energy expenditure models are supported by exercise intervention and accelerometry studies reporting positive correlations between physical activity and total energy expenditure [4] but are challenged by ecological studies in humans and other species showing that more active populations do not have higher total energy expenditure [5-8]. Here we tested a Constrained total energy expenditure model, in which total energy expenditure increases with physical activity at low activity levels but plateaus at higher activity levels as the body adapts to maintain total energy expenditure within a narrow range. We compared total energy expenditure, measured using doubly labeled water, against physical activity, measured using accelerometry, for a large (n = 332) sample of adults living in five populations [9]. After adjusting for body size and composition, total energy expenditure was positively correlated with physical activity, but the relationship was markedly stronger over the lower range of physical activity. For subjects in the upper range of physical activity, total energy expenditure plateaued, supporting a Constrained total energy expenditure model. Body fat percentage and activity intensity appear to modulate the metabolic response to physical activity. Models of energy balance employed in public health [1-3] should be revised to better reflect the constrained nature of total energy expenditure and the complex effects of physical activity on metabolic physiology. PMID:26832439

  18. Extended Practice of a Motor Skill Is Associated with Reduced Metabolic Activity in M1

    PubMed Central

    PICARD, NATHALIE; MATSUZAKA, YOSHIYA; STRICK, PETER L.

    2013-01-01

    How does long-term training and the development of motor skill modify the activity of the primary motor cortex (M1)? To address this issue we trained monkeys for ~1–6 years to perform visually-guided and internally-generated sequences of reaching movements. Then, we used 14C-2-deoxyglucose (2DG) uptake and single neuron recording to measure metabolic and neuron activity in M1. After extended practice, we observed a profound reduction of metabolic activity in M1 for the performance of internally-generated compared to visually-guided tasks. In contrast, measures of neuron firing displayed little difference during the two tasks. These findings suggest that the development of skill through extended practice results in a reduction in the synaptic activity required to produce internally-generated, but not visually-guided sequences of movements. Thus, practice leading to skilled performance results in more efficient generation of neuronal activity in M1. PMID:23912947

  19. Intensity of bouted and sporadic physical activity and the metabolic syndrome in adults

    PubMed Central

    Robson, Jordan

    2015-01-01

    Background. Physical activity guidelines for adults only recognize the health benefits of accumulating bouted moderate-to-vigorous physical activity (MVPA), or MVPA occurring over at least 10 consecutive minutes. There is a lack of evidence supporting the health benefits of other patterns and intensities of activity including sporadic MVPA (i.e., MVPA occurring in periods of fewer than 10 consecutive minutes) and light intensity physical activity (LIPA). The objective of this study was to examine the health benefits associated with physical activity that does not meet the physical activity guidelines criteria for bouted MVPA. Specifically, we examined the association between sporadic MVPA and bouted and sporadic LIPA with the metabolic syndrome. Methods. We studied a representative cross-sectional sample of 1,974 adults aged 20 years and older from the 2003–2006 US National Health and Nutrition Examination Survey. Physical activity was measured over 7 days using Actigraph AM-7164 accelerometers. Each minute over the 7-day measurement period was classified as being of a sedentary, light, or moderate-to-vigorous intensity. A 10 min threshold differentiated bouted activity from sporadic activity. Average minutes/day of sporadic LIPA, sporadic MVPA, bouted LIPA, bouted MVPA, and embedded MVPA (MVPA occurring within bouts of primarily LIPA) were calculated. Metabolic syndrome status was determined using established criteria. Associations were examined using logistic regression and controlled for relevant covariates. Results. For every 30 min/day of physical activity, the odds ratio (95% confidence interval) of the metabolic syndrome was reduced by 4% (1–7%) for bouted LIPA, 64% (51–71%) for bouted MVPA, and 57% (45–67%) for embedded MVPA. Sporadic LIPA was not independently associated with the metabolic syndrome. We could not examine the association between sporadic MVPA and the metabolic syndrome because participants accumulated such a marginal amount of this

  20. Variation in energy expenditure among black-legged kittiwakes: Effects of activity-specific metabolic rates and activity budgets

    USGS Publications Warehouse

    Jodice, P.G.R.; Roby, D.D.; Suryan, R.M.; Irons, D.B.; Kaufman, A.M.; Turco, K.R.; Visser, G.H.

    2003-01-01

    We sought to determine the effect of variation in time-activity budgets (TABs) and foraging behavior on energy expenditure rates of parent black-legged kittiwakes (Rissa tridactyla). We quantified TABs using direct observations of radio-tagged adults and simultaneously measured field metabolic rates (FMR) of these same individuals (n = 20) using the doubly labeled water technique. Estimated metabolic rates of kittiwakes attending their brood at the nest or loafing near the colony were similar (ca. 1.3 x basal metabolic rate [BMR]), although loafing during foraging trips was more costly (2.9 x BMR). Metabolic rates during commuting flight (7.3 x BMR) and prey-searching flight (6.2 x BMR) were similar, while metabolic rates during plunge diving were much higher (ca. 47 x BMR). The proportion of the measurement interval spent foraging had a positive effect on FMR (R2 = 0.68), while the combined proportion of time engaged in nest attendance and loafing near the colony had a negative effect on FMR (R2 = 0.72). Thus, more than two-thirds of the variation in kittiwake FMR could be explained by the allocation of time among various activities. The high energetic cost of plunge diving relative to straight flight and searching flight suggests that kittiwakes can optimize their foraging strategy under conditions of low food availability by commuting long distances to feed in areas where gross foraging efficiency is high.

  1. Potential role for snoRNAs in PKR activation during metabolic stress.

    PubMed

    Youssef, Osama A; Safran, Sarah A; Nakamura, Takahisa; Nix, David A; Hotamisligil, Gökhan S; Bass, Brenda L

    2015-04-21

    Protein kinase RNA-activated (PKR) has long been known to be activated by viral double-stranded RNA (dsRNA) as part of the mammalian immune response. However, in mice PKR is also activated by metabolic stress in the absence of viral infection, and this requires a functional kinase domain, as well as a functional dsRNA-binding domain. The endogenous cellular RNA that potentially leads to PKR activation during metabolic stress is unknown. We investigated this question using mouse embryonic fibroblast cells expressing wild-type PKR (PKRWT) or PKR with a point mutation in each dsRNA-binding motif (PKRRM). Using this system, we identified endogenous RNA that interacts with PKR after induction of metabolic stress by palmitic acid (PA) treatment. Specifically, RIP-Seq analyses showed that the majority of enriched RNAs that interacted with WT PKR (≥twofold, false discovery rate ≤ 5%) were small nucleolar RNAs (snoRNAs). Immunoprecipitation of PKR in extracts of UV-cross-linked cells, followed by RT-qPCR, confirmed that snoRNAs were enriched in PKRWT samples after PA treatment, but not in the PKRRM samples. We also demonstrated that a subset of identified snoRNAs bind and activate PKR in vitro; the presence of a 5'-triphosphate enhanced PKR activity compared with the activity with a 5'-monophosphate, for some, but not all, snoRNAs. Finally, we demonstrated PKR activation in cells upon snoRNA transfection, supporting our hypothesis that endogenous snoRNAs can activate PKR. Our results suggest an unprecedented and unexpected model whereby snoRNAs play a role in the activation of PKR under metabolic stress.

  2. Potential role for snoRNAs in PKR activation during metabolic stress

    PubMed Central

    Youssef, Osama A.; Safran, Sarah A.; Nix, David A.; Hotamisligil, Gökhan S.; Bass, Brenda L.

    2015-01-01

    Protein kinase RNA-activated (PKR) has long been known to be activated by viral double-stranded RNA (dsRNA) as part of the mammalian immune response. However, in mice PKR is also activated by metabolic stress in the absence of viral infection, and this requires a functional kinase domain, as well as a functional dsRNA-binding domain. The endogenous cellular RNA that potentially leads to PKR activation during metabolic stress is unknown. We investigated this question using mouse embryonic fibroblast cells expressing wild-type PKR (PKRWT) or PKR with a point mutation in each dsRNA-binding motif (PKRRM). Using this system, we identified endogenous RNA that interacts with PKR after induction of metabolic stress by palmitic acid (PA) treatment. Specifically, RIP-Seq analyses showed that the majority of enriched RNAs that interacted with WT PKR (≥twofold, false discovery rate ≤ 5%) were small nucleolar RNAs (snoRNAs). Immunoprecipitation of PKR in extracts of UV–cross-linked cells, followed by RT-qPCR, confirmed that snoRNAs were enriched in PKRWT samples after PA treatment, but not in the PKRRM samples. We also demonstrated that a subset of identified snoRNAs bind and activate PKR in vitro; the presence of a 5′-triphosphate enhanced PKR activity compared with the activity with a 5′-monophosphate, for some, but not all, snoRNAs. Finally, we demonstrated PKR activation in cells upon snoRNA transfection, supporting our hypothesis that endogenous snoRNAs can activate PKR. Our results suggest an unprecedented and unexpected model whereby snoRNAs play a role in the activation of PKR under metabolic stress. PMID:25848059

  3. The peroxisome proliferator-activated receptors under epigenetic control in placental metabolism and fetal development.

    PubMed

    Lendvai, Ágnes; Deutsch, Manuel J; Plösch, Torsten; Ensenauer, Regina

    2016-05-15

    The placental metabolism can adapt to the environment throughout pregnancy to both the demands of the fetus and the signals from the mother. Such adaption processes include epigenetic mechanisms, which alter gene expression and may influence the offspring's health. These mechanisms are linked to the diversity of prenatal environmental exposures, including maternal under- or overnutrition or gestational diabetes. The peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that contribute to the developmental plasticity of the placenta by regulating lipid and glucose metabolism pathways, including lipogenesis, steroidogenesis, glucose transporters, and placental signaling pathways, thus representing a link between energy metabolism and reproduction. Among the PPAR isoforms, PPARγ appears to be the main modulator of mammalian placentation. Certain fatty acids and lipid-derived moieties are the natural activating PPAR ligands. By controlling the amounts of maternal nutrients that go across to the fetus, the PPARs play an important regulatory role in placenta metabolism, thereby adapting to the maternal nutritional status. As demonstrated in animal studies, maternal nutrition during gestation can exert long-term influences on the PPAR methylation pattern in offspring organs. This review underlines the current state of knowledge on the relationship between environmental factors and the epigenetic regulation of the PPARs in placenta metabolism and offspring development. PMID:26860983

  4. Temperature, field activity and post-feeding metabolic response in the Asian house gecko, Hemidactylus frenatus.

    PubMed

    Lei, Juan; Booth, David T

    2014-10-01

    Temperature has significant effects on physiological activities and geographical distribution of ectotherms. The Asian house gecko Hemidactylus frenatus has become one of the most widely distributed reptiles in the world and is an invasive species in Australia. Since being introduced into northern Australia, Asian house geckos have spread rapidly and expanded into south-east Queensland and northern New South Wales. Despite their rapid spread, there have been few studies that address thermal adaptability of this species. In order to understand how temperature might limit the distribution and feeding behavior of H. frenatus we observed gecko foraging activities in the wild over the winter period, measured the temperature at which voluntary feeding ceases, and assessed the effect of temperature (30, 25, 20, and 18 °C) on post-feeding metabolic rate. Resting metabolic rate and post-feeding peak in metabolic rate decreased with low temperature, while the duration of elevated metabolic rate after feeding increased at lower temperature. The SDA coefficient (a ratio of the energy expended due to the post-feeding rise in metabolic rate to the energy contained within the meal) did not change systematically with ambient temperature. Field observations and voluntary feeding experiments showed that H. frenatus stop feeding when ambient temperature drops below 17 °C, so that persistent night time temperatures below 17 °C may be limiting the distribution of this species.

  5. Autonomic control of neuronal-astrocytic interactions, regulating metabolic activities, and ion fluxes in the CNS.

    PubMed

    Hertz, L

    1992-01-01

    It is generally assumed that the brain, in contrast to all other organs, is not equipped with an autonomic nervous system, regulating blood supply, and cellular activities. This may be because systemic administration of most drugs acting on monoaminergic or cholinergic receptors have little or no effect on cerebral blood flow and metabolism. However, intrathecal administration of noradrenaline does, indeed, influence both blood flow and energy metabolism in the brain. The present review focuses on effects of noradrenaline or serotonin on energy metabolism, turnover of amino acid transmitters and ion homeostasis, with special emphasis on the cellular localization. Noradrenergic agonists stimulate brain metabolism in vivo as well as many aspects of energy metabolism, Na+,K(+)-ATPase activity and uptake of transmitter amino acids in astrocytes in primary cultures, with little or no effect on corresponding preparations of neurons. Serotonin acts differently, decreasing potassium-induced release of glutamate from both neurons and astrocytes. Little is known about the effects of acetylcholine. The functional significance of these effects is discussed. PMID:1393603

  6. Probing for the Activities of Arsenic and Selenium Metabolizing Microbes

    NASA Astrophysics Data System (ADS)

    Stolz, J. F.

    2007-12-01

    Microbial activities can directly impact the mobility and toxicity of arsenic and selenium in the environment. Arsenic is cycled through oxidation/reduction and methylation/demethylation reactions as part of resistance and respiratory processes. The requirement for selenium is primarily for incorporation into selenocysteine and its function in selenoenzymes. Selenium oxyanions can also serve as an electron acceptor in anaerobic respiration. Both culture and culture-independent methods have been developed to detect the presence and activity of organisms capable of arsenic and selenium transformations. Enrichment media have been successful at cultivating arsenate respiring bacteria from a variety of environments, however, both electron donor and the concentration of arsenic can exert strong selective pressure. Thus, the organisms in the enrichment culture may not be the dominant organisms in the environment. Culture-independent methods, including immunological approaches (e.g., polyclonal antibodies to ArrA) and PCR-based technologies, have also had mixed success. PCR-primers designed to amplify portions of genes involved in resistance (e.g., arsC, acr3), respiration (e.g., arrA), and oxidation (e.g., aoxB) have been useful in several environments. Applications include T-RFLP, rt-PCR, and DGGE analyses. Nevertheless, these primers do not work with certain organisms suggesting the existence of additional enzymes and pathways. Although the biosynthetic pathway (and the proteins involved) for selenocysteine has been described in detail, much less is known about selenium methylation, assimilation and respiration. Only one respiratory selenate reductase has been characterized and its close sequence identity with chlorate and perchlorate reductases has complicated efforts to design a functional probe. Thus many aspects of the biogeochemical cycle of selenium remains to be explored.

  7. L-Arginine Modulates T Cell Metabolism and Enhances Survival and Anti-tumor Activity.

    PubMed

    Geiger, Roger; Rieckmann, Jan C; Wolf, Tobias; Basso, Camilla; Feng, Yuehan; Fuhrer, Tobias; Kogadeeva, Maria; Picotti, Paola; Meissner, Felix; Mann, Matthias; Zamboni, Nicola; Sallusto, Federica; Lanzavecchia, Antonio

    2016-10-20

    Metabolic activity is intimately linked to T cell fate and function. Using high-resolution mass spectrometry, we generated dynamic metabolome and proteome profiles of human primary naive T cells following activation. We discovered critical changes in the arginine metabolism that led to a drop in intracellular L-arginine concentration. Elevating L-arginine levels induced global metabolic changes including a shift from glycolysis to oxidative phosphorylation in activated T cells and promoted the generation of central memory-like cells endowed with higher survival capacity and, in a mouse model, anti-tumor activity. Proteome-wide probing of structural alterations, validated by the analysis of knockout T cell clones, identified three transcriptional regulators (BAZ1B, PSIP1, and TSN) that sensed L-arginine levels and promoted T cell survival. Thus, intracellular L-arginine concentrations directly impact the metabolic fitness and survival capacity of T cells that are crucial for anti-tumor responses.

  8. Relationship between metabolism and radioprotective activity of 2-phenylthiazolidine and its m-bromo derivative

    SciTech Connect

    Fernandez, J.P.; Robbe, Y.; Chapat, J.P.; Chanal, J.L.; Genin, M.; Sentenac-Roumanou, H.; Fatome, M.

    1983-09-01

    Molecular biotransformation of 2-phenylthiazolidine (1) and its m-bromo derivative (2) in the mouse is followed by autoradiographic studies and assessed by analysis of urinary metabolites. Cysteamine (4) is one of the metabolites of compounds 1 and 2. Radioprotective activity and efficacy over a period of time of 1, 2, and 4 correlate closely with distribution and metabolism.

  9. Metabolic Myopathies and Physical Activity: When Fatigue Is More Than Simple Exertion.

    ERIC Educational Resources Information Center

    Tarnopolsky, Mark A.

    2002-01-01

    When patients experience fatigue and muscle cramps beyond exercise adaptation, physicians should consider metabolic myopathies. The most common conditions seen in active patients are myoadenylate deaminase deficiency and disorders such as McArdle's disease. Targeted family histories and basic laboratory studies help rule out conditions mimicking…

  10. CCL5 activation of CCR5 regulates cell metabolism to enhance proliferation of breast cancer cells.

    PubMed

    Gao, Darrin; Rahbar, Ramtin; Fish, Eleanor N

    2016-06-01

    In earlier studies, we showed that CCL5 enhances proliferation and survival of MCF-7 breast cancer cells in an mTOR-dependent manner and we provided evidence that, for T cells, CCL5 activation of CCR5 results in increased glycolysis and enhanced ATP production. Increases in metabolic activity of cancer cells, specifically increased glycolytic activity and increased expression of glucose transporters, are associated with tumour progression. In this report, we provide evidence that CCL5 enhances the proliferation of human breast cancer cell lines (MDA-MB-231, MCF-7) and mouse mammary tumour cells (MMTV-PyMT), mediated by CCR5 activation. Concomitant with enhanced proliferation we show that CCL5 increases cell surface expression of the glucose transporter GLUT1, and increases glucose uptake and ATP production by these cells. Blocking CCL5-inducible glucose uptake abrogates the enhanced proliferation induced by CCL5. We provide evidence that increased glucose uptake is associated with enhanced glycolysis, as measured by extracellular acidification. Moreover, CCL5 enhances the invasive capacity of these breast cancer cells. Using metabolomics, we demonstrate that the metabolic signature of CCL5-treated primary mouse mammary tumour cells reflects increased anabolic metabolism. The implications are that CCL5-CCR5 interactions in the tumour microenvironment regulate metabolic events, specifically glycolysis, to promote tumour proliferation and invasion.

  11. Physical activity, physical fitness, gross motor coordination, and metabolic syndrome: focus of twin research in Portugal.

    PubMed

    Maia, José António Ribeiro; Santos, Daniel; de Freitas, Duarte Luis; Thomis, Martine

    2013-02-01

    A very brief history of Portuguese twin research in sport and human movement sciences is presented. Recruitment procedures, zygosity determination, and phenotypes are given for twins and their parents from the mainland, and Azores and Madeira archipelagos. Preliminary findings are mostly related to physical activity, health-related physical fitness, gross motor coordination, neuromotor development, and metabolic syndrome traits.

  12. Synthesis and evaluation of atorvastatin esters as prodrugs metabolically activated by human carboxylesterases.

    PubMed

    Mizoi, Kenta; Takahashi, Masato; Haba, Masami; Hosokawa, Masakiyo

    2016-02-01

    We synthesized 11 kinds of prodrug with an esterified carboxylic acid moiety of atorvastatin in moderate to high yields. We discovered that they underwent metabolic activation specifically by the human carboxylesterase 1 (CES1) isozyme. The results suggested that these ester compounds of atorvastatin have the potential to act as prodrugs in vivo. PMID:26750256

  13. Biotransformation of anthelmintics and the activity of drug-metabolizing enzymes in the tapeworm Moniezia expansa.

    PubMed

    Prchal, Lukáš; Bártíková, Hana; Bečanová, Aneta; Jirásko, Robert; Vokřál, Ivan; Stuchlíková, Lucie; Skálová, Lenka; Kubíček, Vladimír; Lamka, Jiří; Trejtnar, František; Szotáková, Barbora

    2015-04-01

    The sheep tapeworm Moniezia expansa is very common parasite, which affects ruminants such as sheep, goats as well as other species. The benzimidazole anthelmintics albendazole (ABZ), flubendazole (FLU) and mebendazole (MBZ) are often used to treat the infection. The drug-metabolizing enzymes of helminths may alter the potency of anthelmintic treatment. The aim of our study was to assess the activity of the main drug-metabolizing enzymes and evaluate the metabolism of selected anthelmintics (ABZ, MBZ and FLU) in M. expansa. Activities of biotransformation enzymes were determined in subcellular fractions. Metabolites of the anthelmintics were detected and identified using high performance liquid chromatography/ultra-violet/VIS/fluorescence or ultra-high performance liquid chromatography/mass spectrometry. Reduction of MBZ, FLU and oxidation of ABZ were proved as well as activities of various metabolizing enzymes. Despite the fact that the conjugation enzymes glutathione S-transferase, UDP-glucuronosyl transferase and UDP-glucosyl transferase were active in vitro, no conjugated metabolites of anthelmintics were identified either ex vivo or in vitro. The obtained results indicate that sheep tapeworm is able to deactivate the administered anthelmintics, and thus protects itself against their action.

  14. [The effect of a mite allergen on Na/H metabolic activity in peritoneal mast cells].

    PubMed

    Khlgatian, S V; Pinelis, V G; Berzhets, V M; Strukova, S M

    1992-12-01

    Mite allergen interacting with mast cells treated with sera from bronchial patient sensitized to home dust Dermatophagoides farinae causes changes in intracellular pH. Regulation of pHi peritoneal mast cells is participated by Na/H metabolism probably activated by protein kinase C.

  15. Approaches for minimizing metabolic activation of new drug candidates in drug discovery.

    PubMed

    Kumar, Sanjeev; Mitra, Kaushik; Kassahun, Kelem; Baillie, Thomas A

    2010-01-01

    A large body of circumstantial evidence suggests that metabolic activation of drug candidates to chemically reactive electrophilic metabolites that are capable of covalently modifying cellular macromolecules may result in acute and/or immune system-mediated idiosyncratic toxicities in humans. Thus, minimizing the potential for metabolic activation of new drug candidates during the drug discovery and lead optimization stage represents a prudent strategy to help discover and develop the next generation of safe and effective therapeutic agents. In the present chapter, we discuss the scientific methodologies that currently are available to industrial pharmaceutical scientists for assessing and minimizing metabolic activation during drug discovery, their attributes and limitations, and future scientific directions that have the potential to help advance progress in this field. We also propose a roadmap that should help utilize the armamentarium of available scientific tools in a logical way and contribute to addressing metabolic activation issues in the drug discovery-setting in a rapid, scientifically appropriate, and resource-conscious manner.

  16. CCL5 activation of CCR5 regulates cell metabolism to enhance proliferation of breast cancer cells

    PubMed Central

    Gao, Darrin; Rahbar, Ramtin; Fish, Eleanor N.

    2016-01-01

    In earlier studies, we showed that CCL5 enhances proliferation and survival of MCF-7 breast cancer cells in an mTOR-dependent manner and we provided evidence that, for T cells, CCL5 activation of CCR5 results in increased glycolysis and enhanced ATP production. Increases in metabolic activity of cancer cells, specifically increased glycolytic activity and increased expression of glucose transporters, are associated with tumour progression. In this report, we provide evidence that CCL5 enhances the proliferation of human breast cancer cell lines (MDA-MB-231, MCF-7) and mouse mammary tumour cells (MMTV-PyMT), mediated by CCR5 activation. Concomitant with enhanced proliferation we show that CCL5 increases cell surface expression of the glucose transporter GLUT1, and increases glucose uptake and ATP production by these cells. Blocking CCL5-inducible glucose uptake abrogates the enhanced proliferation induced by CCL5. We provide evidence that increased glucose uptake is associated with enhanced glycolysis, as measured by extracellular acidification. Moreover, CCL5 enhances the invasive capacity of these breast cancer cells. Using metabolomics, we demonstrate that the metabolic signature of CCL5-treated primary mouse mammary tumour cells reflects increased anabolic metabolism. The implications are that CCL5–CCR5 interactions in the tumour microenvironment regulate metabolic events, specifically glycolysis, to promote tumour proliferation and invasion. PMID:27335323

  17. MDC-Analyzer-facilitated combinatorial strategy for improving the activity and stability of halohydrin dehalogenase from Agrobacterium radiobacter AD1.

    PubMed

    Wang, Xiong; Lin, Hao; Zheng, Yu; Feng, Juan; Yang, Zujun; Tang, Lixia

    2015-07-20

    Halohydrin dehalogenase from Agrobacterium radiobacter AD1 (HheC) displays a broad substrate range with high regio- and enantioselectivity of both ring-closure and ring-opening reactions, making the enzyme a useful catalyst for the production of optically pure epoxides and β-substituted alcohols. In this study, we report a novel method using an MDC-Analyzer-facilitated combinatorial strategy to improve the activity and stability of HheC by simultaneously randomizing multiple contiguous residues. Six contiguous active-site residues, which are the hotspots for improving the activity of HheC, were simultaneously selected and randomized using the MDC-Analyzer-facilitated combinatorial strategy, resulting in a high-quality mutagenesis library. After screening a total of 1152 clones, three positive mutants were obtained, which exhibited approximately 3.5-5.9-fold higher kcat values than the wild-type HheC toward 1,3-dichloro-2-propanol (1,3-DCP). However, the inactivation half-life of the best mutant (DG9) at 55 °C decreased 9-fold compared with that of the wild-type HheC. To improve the stability of mutant DG9, seven contiguous potential surface amino acids were revealed by using the B-FITTER tool. Two charged amino acids, Glu and Lys, which are more abundant in thermophilic proteins than in their mesophilic counterparts, were selected to substitute those seven amino acids and were combined together via an MDC-Analyzer-facilitated combinatorial strategy. Two mutants displaying 1.6- and 2.3-fold higher half-life τ1/2 (55 °C) values than their DG9 template were obtained after screening only 384 clones. The results indicated that an MDC-Analyzer-facilitated combinatorial strategy represents an efficient tool for the directed evolution of functional enzymes with multiple contiguous targeting sites.

  18. AMP-activated protein kinase: an emerging drug target to regulate imbalances in lipid and carbohydrate metabolism to treat cardio-metabolic diseases

    PubMed Central

    Srivastava, Rai Ajit K.; Pinkosky, Stephen L.; Filippov, Sergey; Hanselman, Jeffrey C.; Cramer, Clay T.; Newton, Roger S.

    2012-01-01

    The adenosine monophosphate-activated protein kinase (AMPK) is a metabolic sensor of energy metabolism at the cellular as well as whole-body level. It is activated by low energy status that triggers a switch from ATP-consuming anabolic pathways to ATP-producing catabolic pathways. AMPK is involved in a wide range of biological activities that normalizes lipid, glucose, and energy imbalances. These pathways are dysregulated in patients with metabolic syndrome (MetS), which represents a clustering of major cardiovascular risk factors including diabetes, lipid abnormalities, and energy imbalances. Clearly, there is an unmet medical need to find a molecule to treat alarming number of patients with MetS. AMPK, with multifaceted activities in various tissues, has emerged as an attractive drug target to manage lipid and glucose abnormalities and maintain energy homeostasis. A number of AMPK activators have been tested in preclinical models, but many of them have yet to reach to the clinic. This review focuses on the structure-function and role of AMPK in lipid, carbohydrate, and energy metabolism. The mode of action of AMPK activators, mechanism of anti-inflammatory activities, and preclinical and clinical findings as well as future prospects of AMPK as a drug target in treating cardio-metabolic disease are discussed. PMID:22798688

  19. Expression of microRNA-34a in Alzheimer's disease brain targets genes linked to synaptic plasticity, energy metabolism, and resting state network activity.

    PubMed

    Sarkar, S; Jun, S; Rellick, S; Quintana, D D; Cavendish, J Z; Simpkins, J W

    2016-09-01

    Polygenetic risk factors and reduced expression of many genes in late-onset Alzheimer's disease (AD) impedes identification of a target(s) for disease-modifying therapies. We identified a single microRNA, miR-34a that is over expressed in specific brain regions of AD patients as well as in the 3xTg-AD mouse model. Specifically, increased miR-34a expression in the temporal cortex region compared to age matched healthy control correlates with severity of AD pathology. miR-34a over expression in patient's tissue and forced expression in primary neuronal culture correlates with concurrent repression of its target genes involved in synaptic plasticity, oxidative phosphorylation and glycolysis. The repression of oxidative phosphorylation and glycolysis related proteins correlates with reduced ATP production and glycolytic capacity, respectively. We also found that miR-34a overexpressed neurons secrete miR-34a containing exosomes that are taken up by neighboring neurons. Furthermore, miR-34a targets dozens of genes whose expressions are known to be correlated with synchronous activity in resting state functional networks. Our analysis of human genomic sequences from the tentative promoter of miR-34a gene shows the presence of NFκB, STAT1, c-Fos, CREB and p53 response elements. Together, our results raise the possibilities that pathophysiology-induced activation of specific transcription factor may lead to increased expression of miR-34a gene and miR-34a mediated concurrent repression of its target genes in neural networks may result in dysfunction of synaptic plasticity, energy metabolism, and resting state network activity. Thus, our results provide insights into polygenetic AD mechanisms and disclose miR-34a as a potential therapeutic target for AD. PMID:27235866

  20. Sympathetic nervous activation in obesity and the metabolic syndrome--causes, consequences and therapeutic implications.

    PubMed

    Lambert, Gavin W; Straznicky, Nora E; Lambert, Elisabeth A; Dixon, John B; Schlaich, Markus P

    2010-05-01

    The world wide prevalence of obesity and the metabolic syndrome is escalating. Contrary to earlier experimental evidence, human obesity is characterised by sympathetic nervous activation, with the outflows to both the kidney and skeletal muscle being activated. While the mechanisms responsible for initiating the sympathetic activation remain to be unequivocally elucidated, hyperinsulinemia, obstructive sleep apnoea, increased circulating adipokines, stress and beta adrenergic receptor polymorphisms are implicated. The pattern of sympathetic activation may be the pathophysiological mechanism underpinning much obesity-related illnesses with the consequences including, amongst others, the development of hypertension, insulin resistance, diastolic dysfunction and renal impairment. While diet and exercise are the first line therapy for the treatment of obesity and the metabolic syndrome, pharmacological interventions targeting the sympathetic nervous system, either directly or indirectly are also likely to be of benefit. Importantly, the benefit may not necessarily be weight related but may be associated with a reduction in end organ damage.

  1. Cellular Metabolic Activity and the Oxygen and Hydrogen Stable Isotope Composition of Intracellular Water and Metabolites

    NASA Astrophysics Data System (ADS)

    Kreuzer-Martin, H. W.; Hegg, E. L.

    2008-12-01

    Intracellular water is an important pool of oxygen and hydrogen atoms for biosynthesis. Intracellular water is usually assumed to be isotopically identical to extracellular water, but an unexpected experimental result caused us to question this assumption. Heme O isolated from Escherichia coli cells grown in 95% H218O contained only a fraction of the theoretical value of labeled oxygen at a position where the O atom was known to be derived from water. In fact, fewer than half of the oxygen atoms were labeled. In an effort to explain this surprising result, we developed a method to determine the isotope ratios of intracellular water in cultured cells. The results of our experiments showed that during active growth, up to 70% of the oxygen atoms and 50% of the hydrogen atoms in the intracellular water of E. coli are generated during metabolism and can be isotopically distinct from extracellular water. The fraction of isotopically distinct atoms was substantially less in stationary phase and chilled cells, consistent with our hypothesis that less metabolically-generated water would be present in cells with lower metabolic activity. Our results were consistent with and explained the result of the heme O labeling experiment. Only about 40% of the O atoms on the heme O molecule were labeled because, presumably, only about 40% of the water inside the cells was 18O water that had diffused in from the culture medium. The rest of the intracellular water contained 16O atoms derived from either nutrients or atmospheric oxygen. To test whether we could also detect metabolically-derived hydrogen atoms in cellular constituents, we isolated fatty acids from log-phase and stationary phase E. coli and determined the H isotope ratios of individual fatty acids. The results of these experiments showed that environmental water contributed more H atoms to fatty acids isolated in stationary phase than to the same fatty acids isolated from log-phase cells. Stable isotope analyses of

  2. Metabolically active eukaryotic communities in extremely acidic mine drainage.

    PubMed

    Baker, Brett J; Lutz, Michelle A; Dawson, Scott C; Bond, Philip L; Banfield, Jillian F

    2004-10-01

    Acid mine drainage (AMD) microbial communities contain microbial eukaryotes (both fungi and protists) that confer a biofilm structure and impact the abundance of bacteria and archaea and the community composition via grazing and other mechanisms. Since prokaryotes impact iron oxidation rates and thus regulate AMD generation rates, it is important to analyze the fungal and protistan populations. We utilized 18S rRNA and beta-tubulin gene phylogenies and fluorescent rRNA-specific probes to characterize the eukaryotic diversity and distribution in extremely acidic (pHs 0.8 to 1.38), warm (30 to 50 degrees C), metal-rich (up to 269 mM Fe(2+), 16.8 mM Zn, 8.5 mM As, and 4.1 mM Cu) AMD solutions from the Richmond Mine at Iron Mountain, Calif. A Rhodophyta (red algae) lineage and organisms from the Vahlkampfiidae family were identified. The fungal 18S rRNA and tubulin gene sequences formed two distinct phylogenetic groups associated with the classes Dothideomycetes and Eurotiomycetes. Three fungal isolates that were closely related to the Dothideomycetes clones were obtained. We suggest the name "Acidomyces richmondensis" for these isolates. Since these ascomycete fungi were morphologically indistinguishable, rRNA-specific oligonucleotide probes were designed to target the Dothideomycetes and Eurotiomycetes via fluorescent in situ hybridization (FISH). FISH analyses indicated that Eurotiomycetes are generally more abundant than Dothideomycetes in all of the seven locations studied within the Richmond Mine system. This is the first study to combine the culture-independent detection of fungi with in situ detection and a demonstration of activity in an acidic environment. The results expand our understanding of the subsurface AMD microbial community structure.

  3. Heat stress has an effect on motility and metabolic activity of rabbit spermatozoa.

    PubMed

    Sabés-Alsina, Maria; Tallo-Parra, Oriol; Mogas, Maria Teresa; Morrell, Jane M; Lopez-Bejar, Manel

    2016-10-01

    In the warm months the function of the spermatozoa can be affected by the temperature of the reproductive tract of the female exposed to hyperthermic conditions. The aim of this study was to evaluate the impact of heat stress on sperm parameters in an in vitro model and to determine if there were seasonal effects on sperm heat tolerance. Sperm samples from 32 New Zealand White rabbits were collected in two seasons and incubated at scrotal (32.5°C), body (37°C) or hyperthermic (42°C) temperatures for 3h. Sperm viability and morphology were evaluated using nigrosin-eosin staining. Motility and metabolic activity parameters were determined using computer-assisted sperm analysis and the QBlue cell viability test, respectively. The incubation of spermatozoa at 42°C decreased (P<0.05) the mean values of total motility, curvilinear (VCL) and mean velocity (VAP) as well as the metabolic activity with respect to the incubation at 32.5°C and 37°C. No seasonal effects were observed except for the highest percentages of bent and coiled tails in the cold season, and the highest mean values of VCL, linear velocity and VAP in the warm season (P<0.01). The interaction between in vitro heat stress and season was significant for metabolic activity (P=0.02). Our results suggest that rabbit spermatozoa parameters are largely modified by a short exposure to hyperthermic conditions, in terms of metabolic activity and motility parameters. Thus, a short exposure of spermatozoa to an environment of 42°C in temperature for only 3h may compromise sperm functionality. Additionally, sperm metabolic activity is influenced by season. PMID:27530369

  4. The MurE synthetase from Thermotoga maritima is endowed with an unusual D-lysine adding activity.

    PubMed

    Boniface, Audrey; Bouhss, Ahmed; Mengin-Lecreulx, Dominique; Blanot, Didier

    2006-06-01

    The peptidoglycan of Thermotoga maritima, an extremely thermophilic eubacterium, was shown to contain no diaminopimelic acid and approximate amounts of both enantiomers of lysine (Huber, R., Langworthy, T. A., König, H., Thomm, M., Woese, C. R., Sleytr, U. B., and Stetter, K. O. (1986) Arch. Microbiol. 144, 324-333). To assess the possible involvement of the MurE activity in the incorporation of D-lysine, the murE gene from this organism was cloned in Escherichia coli, and the corresponding protein was purified as the C-terminal His6-tagged form. In vitro assays showed that D-lysine and meso-diaminopimelic acid were added to UDP-N-acetylmuramoyl-dipeptide with 25 and 10% efficiencies, respectively, relative to L-lysine. The purified enzyme was used to synthesize the L- and D-lysine-containing UDP-N-acetylmuramoyl-tripeptides; chemical analysis revealed an unusual structure for the D-lysine-containing nucleotide, namely acylation of the epsilon-amino function of D-lysine by the D-glutamyl residue. In vitro assays with MurF and MraY enzymes from T. maritima showed that this novel nucleotide was not a substrate for MurF but that it could be directly processed into tripeptide lipid I by MraY, thereby substantiating the role of MurE in the incorporation of D-lysine into peptidoglycan.

  5. Cardiovascular, Metabolic Effects and Dietary Composition of Ad-Libitum Paleolithic vs. Australian Guide to Healthy Eating Diets: A 4-Week Randomised Trial.

    PubMed

    Genoni, Angela; Lyons-Wall, Philippa; Lo, Johnny; Devine, Amanda

    2016-01-01

    (1) BACKGROUND: The Paleolithic diet is popular in Australia, however, limited literature surrounds the dietary pattern. Our primary aim was to compare the Paleolithic diet with the Australian Guide to Healthy Eating (AGHE) in terms of anthropometric, metabolic and cardiovascular risk factors, with a secondary aim to examine the macro and micronutrient composition of both dietary patterns; (2) METHODS: 39 healthy women (mean ± SD age 47 ± 13 years, BMI 27 ± 4 kg/m²) were randomised to either the Paleolithic (n = 22) or AGHE diet (n = 17) for four weeks. Three-day weighed food records, body composition and biochemistry data were collected pre and post intervention; (3) RESULTS: Significantly greater weight loss occurred in the Paleolithic group (-1.99 kg, 95% CI -2.9, -1.0), p < 0.001). There were no differences in cardiovascular and metabolic markers between groups. The Paleolithic group had lower intakes of carbohydrate (-14.63% of energy (E), 95% CI -19.5, -9.7), sodium (-1055 mg/day, 95% CI -1593, -518), calcium (-292 mg/day 95% CI -486.0, -99.0) and iodine (-47.9 μg/day, 95% CI -79.2, -16.5) and higher intakes of fat (9.39% of E, 95% CI 3.7, 15.1) and β-carotene (6777 μg/day 95% CI 2144, 11410) (all p < 0.01); (4) CONCLUSIONS: The Paleolithic diet induced greater changes in body composition over the short-term intervention, however, larger studies are recommended to assess the impact of the Paleolithic vs. AGHE diets on metabolic and cardiovascular risk factors in healthy populations. PMID:27223304

  6. Cardiovascular, Metabolic Effects and Dietary Composition of Ad-Libitum Paleolithic vs. Australian Guide to Healthy Eating Diets: A 4-Week Randomised Trial

    PubMed Central

    Genoni, Angela; Lyons-Wall, Philippa; Lo, Johnny; Devine, Amanda

    2016-01-01

    (1) Background: The Paleolithic diet is popular in Australia, however, limited literature surrounds the dietary pattern. Our primary aim was to compare the Paleolithic diet with the Australian Guide to Healthy Eating (AGHE) in terms of anthropometric, metabolic and cardiovascular risk factors, with a secondary aim to examine the macro and micronutrient composition of both dietary patterns; (2) Methods: 39 healthy women (mean ± SD age 47 ± 13 years, BMI 27 ± 4 kg/m2) were randomised to either the Paleolithic (n = 22) or AGHE diet (n = 17) for four weeks. Three-day weighed food records, body composition and biochemistry data were collected pre and post intervention; (3) Results: Significantly greater weight loss occurred in the Paleolithic group (−1.99 kg, 95% CI −2.9, −1.0), p < 0.001). There were no differences in cardiovascular and metabolic markers between groups. The Paleolithic group had lower intakes of carbohydrate (−14.63% of energy (E), 95% CI −19.5, −9.7), sodium (−1055 mg/day, 95% CI −1593, −518), calcium (−292 mg/day 95% CI −486.0, −99.0) and iodine (−47.9 μg/day, 95% CI −79.2, −16.5) and higher intakes of fat (9.39% of E, 95% CI 3.7, 15.1) and β-carotene (6777 μg/day 95% CI 2144, 11410) (all p < 0.01); (4) Conclusions: The Paleolithic diet induced greater changes in body composition over the short-term intervention, however, larger studies are recommended to assess the impact of the Paleolithic vs. AGHE diets on metabolic and cardiovascular risk factors in healthy populations. PMID:27223304

  7. Do obese but metabolically normal women differ in intra-abdominal fat and physical activity levels from those with the expected metabolic abnormalities? A cross-sectional study

    PubMed Central

    2010-01-01

    Background Obesity remains a major public health problem, associated with a cluster of metabolic abnormalities. However, individuals exist who are very obese but have normal metabolic parameters. The aim of this study was to determine to what extent differences in metabolic health in very obese women are explained by differences in body fat distribution, insulin resistance and level of physical activity. Methods This was a cross-sectional pilot study of 39 obese women (age: 28-64 yrs, BMI: 31-67 kg/m2) recruited from community settings. Women were defined as 'metabolically normal' on the basis of blood glucose, lipids and blood pressure. Magnetic Resonance Imaging was used to determine body fat distribution. Detailed lifestyle and metabolic profiles of participants were obtained. Results Women with a healthy metabolic profile had lower intra-abdominal fat volume (geometric mean 4.78 l [95% CIs 3.99-5.73] vs 6.96 l [5.82-8.32]) and less insulin resistance (HOMA 3.41 [2.62-4.44] vs 6.67 [5.02-8.86]) than those with an abnormality. The groups did not differ in abdominal subcutaneous fat volume (19.6 l [16.9-22.7] vs 20.6 [17.6-23.9]). A higher proportion of those with a healthy compared to a less healthy metabolic profile met current physical activity guidelines (70% [95% CIs 55.8-84.2] vs 25% [11.6-38.4]). Intra-abdominal fat, insulin resistance and physical activity make independent contributions to metabolic status in very obese women, but explain only around a third of the variance. Conclusion A sub-group of women exists who are metabolically normal despite being very obese. Differences in fat distribution, insulin resistance, and physical activity level are associated with metabolic differences in these women, but account only partially for these differences. Future work should focus on strategies to identify those obese individuals most at risk of the negative metabolic consequences of obesity and on identifying other factors that contribute to metabolic status

  8. Decreased food intake rather than zinc deficiency is associated with changes in plasma leptin, metabolic rate, and activity levels in zinc deficient rats( small star, filled).

    PubMed

    Gaetke, Lisa M.; Frederich, Robert C.; Oz, Helieh S.; McClain, Craig J.

    2002-04-01

    This study investigated the hypothesis that the reduced food intake and poor weight gain in zinc deficient rats is due to: increased plasma leptin concentration, increased physical activity and/or increased metabolic rate. Weanling rats were assigned to three groups: controls fed ad libitum (C), zinc deficient (ZD), and pair-fed controls (PF), and tested in a metabolic chamber and activity monitor at baseline and weekly for four weeks. At the end of the study, all groups were compared for differences in plasma leptin concentrations. ZD and PF animals had markedly reduced food intake and weight gain. ZD had reduced stereotypic and locomotor activity compared to PF animals and both groups demonstrated an abolished peri-nocturnal activity spike and were much less active than controls. This was associated with a reduced total metabolic rate by day 30: ZD (0.73 +/- 0.07 kcal/hr, p = 0.0001) and PF (0.83 +/- 0.06 kcal/hr, p = 0.0001) groups vs. controls (1.82 +/- 0.09 kcal/hr). Plasma leptin concentrations in ZD (1.55 +/- 0.06 &mgr;g/L) were lower than controls (2.01 +/- 0.18 &mgr;g/L, p < 0.03), but neither ZD nor controls were statistically different from PF (1.68 +/- 0.05 &mgr;g/L). Both low leptin concentrations and low metabolic rates in the ZD and PF rats were associated with decreased food intake rather than zinc deficiency. The reduced food intake and poor weight gain observed in zinc deficient rats could not be explained by elevated leptin concentrations, hypermetabolism, or increased activity. Low serum leptin concentrations, hypometabolism, and decreased activity are more likely the result of the anorexia of zinc deficiency.

  9. Metabolic maintenance of cell asymmetry following division in activated T lymphocytes.

    PubMed

    Verbist, Katherine C; Guy, Cliff S; Milasta, Sandra; Liedmann, Swantje; Kamiński, Marcin M; Wang, Ruoning; Green, Douglas R

    2016-04-21

    Asymmetric cell division, the partitioning of cellular components in response to polarizing cues during mitosis, has roles in differentiation and development. It is important for the self-renewal of fertilized zygotes in Caenorhabditis elegans and neuroblasts in Drosophila, and in the development of mammalian nervous and digestive systems. T lymphocytes, upon activation by antigen-presenting cells (APCs), can undergo asymmetric cell division, wherein the daughter cell proximal to the APC is more likely to differentiate into an effector-like T cell and the distal daughter is more likely to differentiate into a memory-like T cell. Upon activation and before cell division, expression of the transcription factor c-Myc drives metabolic reprogramming, necessary for the subsequent proliferative burst. Here we find that during the first division of an activated T cell in mice, c-Myc can sort asymmetrically. Asymmetric distribution of amino acid transporters, amino acid content, and activity of mammalian target of rapamycin complex 1 (mTORC1) is correlated with c-Myc expression, and both amino acids and mTORC1 activity sustain the differences in c-Myc expression in one daughter cell compared to the other. Asymmetric c-Myc levels in daughter T cells affect proliferation, metabolism, and differentiation, and these effects are altered by experimental manipulation of mTORC1 activity or c-Myc expression. Therefore, metabolic signalling pathways cooperate with transcription programs to maintain differential cell fates following asymmetric T-cell division.

  10. Impact of bariatric surgery on carotid artery inflammation and the metabolic activity in different adipose tissues.

    PubMed

    Bucerius, Jan; Vijgen, Guy H E J; Brans, Boudewijn; Bouvy, Nicole D; Bauwens, Matthias; Rudd, James H F; Havekes, Bas; Fayad, Zahi A; van Marken Lichtenbelt, Wouter D; Mottaghy, Felix M

    2015-05-01

    In this study, we unravel a molecular imaging marker correlated with the known reduction of cardiovascular events (most commonly related to vulnerable plaques) in morbidly obese patients after bariatric surgery (BaS).We prospectively imaged 10 morbidly obese subjects with F-fluorodeoxyglucose (F-FDG) positron emission tomography/computed tomography before and 1 year after BaS. F-FDG uptake-which is enhanced in inflamed, atherosclerotic vessels and in metabolically active adipose tissues-was quantified in the carotids, pericardial adipose tissue (PAT), visceral adipose tissue (VAT), as well as brown adipose tissue (BAT). The degree of carotid inflammation was compared to lean and overweight controls.Carotid inflammation significantly declined leading to an F-FDG uptake comparable to the 2 control groups. Metabolic activity significantly decreased in PAT and VAT and increased in BAT.BaS leads to a normalization of carotid artery inflammation and a beneficial impact on the metabolic activity in PAT, VAT, and BAT that is related to the metabolic syndrome observed in this patient group.

  11. MFN1 deacetylation activates adaptive mitochondrial fusion and protects metabolically challenged mitochondria.

    PubMed

    Lee, Joo-Yong; Kapur, Meghan; Li, Ming; Choi, Moon-Chang; Choi, Sujin; Kim, Hak-June; Kim, Inhye; Lee, Eunji; Taylor, J Paul; Yao, Tso-Pang

    2014-11-15

    Fasting and glucose shortage activate a metabolic switch that shifts more energy production to mitochondria. This metabolic adaptation ensures energy supply, but also elevates the risk of mitochondrial oxidative damage. Here, we present evidence that metabolically challenged mitochondria undergo active fusion to suppress oxidative stress. In response to glucose starvation, mitofusin 1 (MFN1) becomes associated with the protein deacetylase HDAC6. This interaction leads to MFN1 deacetylation and activation, promoting mitochondrial fusion. Deficiency in HDAC6 or MFN1 prevents mitochondrial fusion induced by glucose deprivation. Unexpectedly, failure to undergo fusion does not acutely affect mitochondrial adaptive energy production; instead, it causes excessive production of mitochondrial reactive oxygen species and oxidative damage, a defect suppressed by an acetylation-resistant MFN1 mutant. In mice subjected to fasting, skeletal muscle mitochondria undergo dramatic fusion. Remarkably, fasting-induced mitochondrial fusion is abrogated in HDAC6-knockout mice, resulting in extensive mitochondrial degeneration. These findings show that adaptive mitochondrial fusion protects metabolically challenged mitochondria.

  12. Species differences in intestinal metabolic activities of cytochrome P450 isoforms between cynomolgus monkeys and humans.

    PubMed

    Nishimuta, Haruka; Sato, Kimihiko; Mizuki, Yasuyuki; Yabuki, Masashi; Komuro, Setsuko

    2011-06-01

    The oral bioavailability of some drugs is markedly lower in cynomolgus monkeys than in humans. One of the reasons for the low bioavailability in cynomolgus monkeys may be the higher metabolic activity of intestinal CYP3A; however, the species differences in intestinal metabolic activities of other CYP isoforms between cynomolgus monkeys and humans are not well known. In the present study, we investigated the intrinsic clearance (CL(int)) values in pooled intestinal microsomes from cynomolgus monkeys and humans using 25 substrates of human CYP1A2, CYP2J2, CYP2C, and CYP2D6. As in humans, intestinal CL(int) values of human CYP1A2 and CYP2D6 substrates in cynomolgus monkeys were low. On the other hand, intestinal CL(int) values of human CYP2J2 and CYP2C substrates in cynomolgus monkeys were greatly higher than those in humans. Using immunoinhibitory antibodies and chemical inhibitors, we showed that the higher intestinal CL(int) values of the human CYP2J2 and CYP2C substrates in cynomolgus monkeys might be caused by monkey CYP4F and CYP2C subfamily members, respectively. In conclusion, there is a possibility that the greatly higher metabolic activity of CYP2C and CYP4F in cynomolgus monkey intestine is one of the causes of the species difference of intestinal first-pass metabolism between cynomolgus monkeys and humans. PMID:21383522

  13. AMP-Activated Protein Kinase Regulates Oxidative Metabolism in Caenorhabditis elegans through the NHR-49 and MDT-15 Transcriptional Regulators.

    PubMed

    Moreno-Arriola, Elizabeth; El Hafidi, Mohammed; Ortega-Cuéllar, Daniel; Carvajal, Karla

    2016-01-01

    Cellular energy regulation relies on complex signaling pathways that respond to fuel availability and metabolic demands. Dysregulation of these networks is implicated in the development of human metabolic diseases such as obesity and metabolic syndrome. In Caenorhabditis elegans the AMP-activated protein kinase, AAK, has been associated with longevity and stress resistance; nevertheless its precise role in energy metabolism remains elusive. In the present study, we find an evolutionary conserved role of AAK in oxidative metabolism. Similar to mammals, AAK is activated by AICAR and metformin and leads to increased glycolytic and oxidative metabolic fluxes evidenced by an increase in lactate levels and mitochondrial oxygen consumption and a decrease in total fatty acids and lipid storage, whereas augmented glucose availability has the opposite effects. We found that these changes were largely dependent on the catalytic subunit AAK-2, since the aak-2 null strain lost the observed metabolic actions. Further results demonstrate that the effects due to AAK activation are associated to SBP-1 and NHR-49 transcriptional factors and MDT-15 transcriptional co-activator, suggesting a regulatory pathway that controls oxidative metabolism. Our findings establish C. elegans as a tractable model system to dissect the relationship between distinct molecules that play a critical role in the regulation of energy metabolism in human metabolic diseases.

  14. AMP-Activated Protein Kinase Regulates Oxidative Metabolism in Caenorhabditis elegans through the NHR-49 and MDT-15 Transcriptional Regulators

    PubMed Central

    Moreno-Arriola, Elizabeth; EL Hafidi, Mohammed; Ortega-Cuéllar, Daniel; Carvajal, Karla

    2016-01-01

    Cellular energy regulation relies on complex signaling pathways that respond to fuel availability and metabolic demands. Dysregulation of these networks is implicated in the development of human metabolic diseases such as obesity and metabolic syndrome. In Caenorhabditis elegans the AMP-activated protein kinase, AAK, has been associated with longevity and stress resistance; nevertheless its precise role in energy metabolism remains elusive. In the present study, we find an evolutionary conserved role of AAK in oxidative metabolism. Similar to mammals, AAK is activated by AICAR and metformin and leads to increased glycolytic and oxidative metabolic fluxes evidenced by an increase in lactate levels and mitochondrial oxygen consumption and a decrease in total fatty acids and lipid storage, whereas augmented glucose availability has the opposite effects. We found that these changes were largely dependent on the catalytic subunit AAK-2, since the aak-2 null strain lost the observed metabolic actions. Further results demonstrate that the effects due to AAK activation are associated to SBP-1 and NHR-49 transcriptional factors and MDT-15 transcriptional co-activator, suggesting a regulatory pathway that controls oxidative metabolism. Our findings establish C. elegans as a tractable model system to dissect the relationship between distinct molecules that play a critical role in the regulation of energy metabolism in human metabolic diseases. PMID:26824904

  15. AMP-Activated Protein Kinase Regulates Oxidative Metabolism in Caenorhabditis elegans through the NHR-49 and MDT-15 Transcriptional Regulators.

    PubMed

    Moreno-Arriola, Elizabeth; El Hafidi, Mohammed; Ortega-Cuéllar, Daniel; Carvajal, Karla

    2016-01-01

    Cellular energy regulation relies on complex signaling pathways that respond to fuel availability and metabolic demands. Dysregulation of these networks is implicated in the development of human metabolic diseases such as obesity and metabolic syndrome. In Caenorhabditis elegans the AMP-activated protein kinase, AAK, has been associated with longevity and stress resistance; nevertheless its precise role in energy metabolism remains elusive. In the present study, we find an evolutionary conserved role of AAK in oxidative metabolism. Similar to mammals, AAK is activated by AICAR and metformin and leads to increased glycolytic and oxidative metabolic fluxes evidenced by an increase in lactate levels and mitochondrial oxygen consumption and a decrease in total fatty acids and lipid storage, whereas augmented glucose availability has the opposite effects. We found that these changes were largely dependent on the catalytic subunit AAK-2, since the aak-2 null strain lost the observed metabolic actions. Further results demonstrate that the effects due to AAK activation are associated to SBP-1 and NHR-49 transcriptional factors and MDT-15 transcriptional co-activator, suggesting a regulatory pathway that controls oxidative metabolism. Our findings establish C. elegans as a tractable model system to dissect the relationship between distinct molecules that play a critical role in the regulation of energy metabolism in human metabolic diseases. PMID:26824904

  16. Role of lipids in the metabolism and activation of immune cells.

    PubMed

    Hubler, Merla J; Kennedy, Arion J

    2016-08-01

    Immune cell plasticity has extensive implications in the pathogenesis and resolution of metabolic disorders, cancers, autoimmune diseases and chronic inflammatory disorders. Over the past decade, nutritional status has been discovered to influence the immune response. In metabolic disorders such as obesity, immune cells interact with various classes of lipids, which are capable of controlling the plasticity of macrophages and T lymphocytes. The purpose of this review is to discuss lipids and their impact on innate and adaptive immune responses, focusing on two areas: (1) the impact of altering lipid metabolism on immune cell activation, differentiation and function and (2) the mechanism by which lipids such as cholesterol and fatty acids regulate immune cell plasticity.

  17. NF-Y activates genes of metabolic pathways altered in cancer cells.

    PubMed

    Benatti, Paolo; Chiaramonte, Maria Luisa; Lorenzo, Mariangela; Hartley, John A; Hochhauser, Daniel; Gnesutta, Nerina; Mantovani, Roberto; Imbriano, Carol; Dolfini, Diletta

    2016-01-12

    The trimeric transcription factor NF-Y binds to the CCAAT box, an element enriched in promoters of genes overexpressed in tumors. Previous studies on the NF-Y regulome identified the general term metabolism as significantly enriched. We dissect here in detail the targeting of metabolic genes by integrating analysis of NF-Y genomic binding and profilings after inactivation of NF-Y subunits in different cell types. NF-Y controls de novo biosynthetic pathways of lipids, teaming up with the master SREBPs regulators. It activates glycolytic genes, but, surprisingly, is neutral or represses mitochondrial respiratory genes. NF-Y targets the SOCG (Serine, One Carbon, Glycine) and Glutamine pathways, as well as genes involved in the biosynthesis of polyamines and purines. Specific cancer-driving nodes are generally under NF-Y control. Altogether, these data delineate a coherent strategy to promote expression of metabolic genes fuelling anaerobic energy production and other anabolic pathways commonly altered in cancer cells.

  18. Susceptibility of Candida albicans biofilms to caspofungin and anidulafungin is not affected by metabolic activity or biomass production.

    PubMed

    Marcos-Zambrano, Laura Judith; Escribano, Pilar; Bouza, Emilio; Guinea, Jesús

    2016-02-01

    Micafungin is more active against biofilms with high metabolic activity; however, it is unknown whether this observation applies to caspofungin and anidulafungin and whether it is also dependent on the biomass production. We compare the antifungal activity of anidulafungin, caspofungin, and micafungin against preformed Candida albicans biofilms with different degrees of metabolic activity and biomass production from 301 isolates causing fungemia in patients admitted to Gregorio Marañon Hospital (January 2007 to September 2014). Biofilms were classified as having low, moderate, or high metabolic activity according XTT reduction assay or having low, moderate, or high biomass according to crystal violet assay. Echinocandin MICs for planktonic and sessile cells were measured using the EUCAST E.Def 7.2 procedure and XTT reduction assay, respectively. Micafungin showed the highest activity against biofilms classified according to the metabolic activity and biomass production (P < .001). The activity of caspofungin and anidulafungin was not dependent on the metabolic activity of the biofilm or the biomass production. These observations were confirmed by scanning electron microscopy. None of the echinocandins produced major changes in the structure of biofilms with low metabolic activity and biomass production when compared with the untreated biofilms. However, biofilm with high metabolic activity or high biomass production was considerably more susceptible to micafungin; this effect was not shown by caspofungin or anidulafungin. PMID:26543157

  19. Susceptibility of Candida albicans biofilms to caspofungin and anidulafungin is not affected by metabolic activity or biomass production.

    PubMed

    Marcos-Zambrano, Laura Judith; Escribano, Pilar; Bouza, Emilio; Guinea, Jesús

    2016-02-01

    Micafungin is more active against biofilms with high metabolic activity; however, it is unknown whether this observation applies to caspofungin and anidulafungin and whether it is also dependent on the biomass production. We compare the antifungal activity of anidulafungin, caspofungin, and micafungin against preformed Candida albicans biofilms with different degrees of metabolic activity and biomass production from 301 isolates causing fungemia in patients admitted to Gregorio Marañon Hospital (January 2007 to September 2014). Biofilms were classified as having low, moderate, or high metabolic activity according XTT reduction assay or having low, moderate, or high biomass according to crystal violet assay. Echinocandin MICs for planktonic and sessile cells were measured using the EUCAST E.Def 7.2 procedure and XTT reduction assay, respectively. Micafungin showed the highest activity against biofilms classified according to the metabolic activity and biomass production (P < .001). The activity of caspofungin and anidulafungin was not dependent on the metabolic activity of the biofilm or the biomass production. These observations were confirmed by scanning electron microscopy. None of the echinocandins produced major changes in the structure of biofilms with low metabolic activity and biomass production when compared with the untreated biofilms. However, biofilm with high metabolic activity or high biomass production was considerably more susceptible to micafungin; this effect was not shown by caspofungin or anidulafungin.

  20. Metabolic Cost of Daily Activities and Effect of Mobility Impairment in Older Adults

    PubMed Central

    Knaggs, Jeffrey D; Larkin, Kelly A; Manini, Todd M

    2013-01-01

    OBJECTIVES There is a shortage of information on metabolic costs of daily physical activities in older adults and the effect of having mobility impairments. The primary purpose of this study was to evaluate metabolic equivalent (MET) values on common daily tasks in men and women aged > 70 years compared to normative criteria. A secondary purpose was to determine the effect of having mobility impairments. DESIGN Cross-sectional observational study. SETTING University based research clinic PARTICIPANTS Forty-five participants aged 70 to 90 years of age (mean: 76.3 ± 5.1) volunteered to complete 17 daily activities, each lasting 10 minutes. MEASUREMENTS Oxygen consumption (VO2 = ml•kg−1•min−1) was measured through a mask by a portable gas analyzer and MET values were calculated as measured VO2/3.5 ml•kg−1•min−1. Values were compared to both normative values and between participants with and without mobility impairments. RESULTS Compared to the established normative criteria, measured METs were different in 14 of 17 tasks performed. Compared to measured METs, normative values underestimated walking leisurely (0.87 ± 0.12 METs) walking briskly (0.87 ± 0.12 METs ), and bed making (1.07 ± 0.10 METs ), but overestimated gardening (1.46 ± 0.12 METs) and climbing stairs (0.73 ± 0.18). Participants with impairments had significantly lower METs while gardening, vacuuming/sweeping, stair climbing, and walking briskly. However, when METs were adjusted for performance speed the metabolic costs were 16–27% higher for those with mobility impairments. CONCLUSION Compared to normative values, metabolic costs of daily activities are substantially different in older adults and having mobility impairments increases this metabolic cost. These results may have implications for practitioners to appropriately prescribe daily physical activities for healthy and mobility impaired older adults. PMID:22091979

  1. Effects of fluoride emissions on enzyme activity in metabolism of agricultural plants

    SciTech Connect

    Moeri, P.B.

    1980-01-01

    The effects of fluoride on the activity of malatedehydrogenase (MDH) in rape seed and rye grass have been investigated. Fluoride, which has been absorbed from the air, seems to act differently from fluoride added to the soil. The action of airborne fluoride compounds resorbed by the plant on the activity of MDH significantly correlated with the distance from an aluminum plant, crop yield, and fluoride content. 5 references, 5 figures, 2 tables.

  2. Akt-mTORC1 signaling regulates Acly to integrate metabolic input to control of macrophage activation

    PubMed Central

    Covarrubias, Anthony J; Aksoylar, Halil Ibrahim; Yu, Jiujiu; Snyder, Nathaniel W; Worth, Andrew J; Iyer, Shankar S; Wang, Jiawei; Ben-Sahra, Issam; Byles, Vanessa; Polynne-Stapornkul, Tiffany; Espinosa, Erika C; Lamming, Dudley; Manning, Brendan D; Zhang, Yijing; Blair, Ian A; Horng, Tiffany

    2016-01-01

    Macrophage activation/polarization to distinct functional states is critically supported by metabolic shifts. How polarizing signals coordinate metabolic and functional reprogramming, and the potential implications for control of macrophage activation, remains poorly understood. Here we show that IL-4 signaling co-opts the Akt-mTORC1 pathway to regulate Acly, a key enzyme in Ac-CoA synthesis, leading to increased histone acetylation and M2 gene induction. Only a subset of M2 genes is controlled in this way, including those regulating cellular proliferation and chemokine production. Moreover, metabolic signals impinge on the Akt-mTORC1 axis for such control of M2 activation. We propose that Akt-mTORC1 signaling calibrates metabolic state to energetically demanding aspects of M2 activation, which may define a new role for metabolism in supporting macrophage activation. DOI: http://dx.doi.org/10.7554/eLife.11612.001 PMID:26894960

  3. Indole and Tryptophan Metabolism: Endogenous and Dietary Routes to Ah Receptor Activation

    PubMed Central

    Hubbard, Troy D.; Murray, Iain A.

    2015-01-01

    The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor recognized for its role in xenobiotic metabolism. The physiologic function of AHR has expanded to include roles in immune regulation, organogenesis, mucosal barrier function, and the cell cycle. These functions are likely dependent upon ligand-mediated activation of the receptor. High-affinity ligands of AHR have been classically defined as xenobiotics, such as polychlorinated biphenyls and dioxins. Identification of endogenous AHR ligands is key to understanding the physiologic functions of this enigmatic receptor. Metabolic pathways targeting the amino acid tryptophan and indole can lead to a myriad of metabolites, some of which are AHR ligands. Many of these ligands exhibit species selective preferential binding to AHR. The discovery of specific tryptophan metabolites as AHR ligands may provide insight concerning where AHR is activated in an organism, such as at the site of inflammation and within the intestinal tract. PMID:26041783

  4. Genome-scale metabolic modeling to provide insight into the production of storage compounds during feast-famine cycles of activated sludge.

    PubMed

    Tajparast, Mohammad; Frigon, Dominic

    2013-01-01

    Studying storage metabolism during feast-famine cycles of activated sludge treatment systems provides profound insight in terms of both operational issues (e.g., foaming and bulking) and process optimization for the production of value added by-products (e.g., bioplastics). We examined the storage metabolism (including poly-β-hydroxybutyrate [PHB], glycogen, and triacylglycerols [TAGs]) during feast-famine cycles using two genome-scale metabolic models: Rhodococcus jostii RHA1 (iMT1174) and Escherichia coli K-12 (iAF1260) for growth on glucose, acetate, and succinate. The goal was to develop the proper objective function (OF) for the prediction of the main storage compound produced in activated sludge for given feast-famine cycle conditions. For the flux balance analysis, combinations of three OFs were tested. For all of them, the main OF was to maximize growth rates. Two additional sub-OFs were used: (1) minimization of biochemical fluxes, and (2) minimization of metabolic adjustments (MoMA) between the feast and famine periods. All (sub-)OFs predicted identical substrate-storage associations for the feast-famine growth of the above-mentioned metabolic models on a given substrate when glucose and acetate were set as sole carbon sources (i.e., glucose-glycogen and acetate-PHB), in agreement with experimental observations. However, in the case of succinate as substrate, the predictions depended on the network structure of the metabolic models such that the E. coli model predicted glycogen accumulation and the R. jostii model predicted PHB accumulation. While the accumulation of both PHB and glycogen was observed experimentally, PHB showed higher dynamics during an activated sludge feast-famine growth cycle with succinate as substrate. These results suggest that new modeling insights between metabolic predictions and population ecology will be necessary to properly predict metabolisms likely to emerge within the niches of activated sludge communities. Nonetheless

  5. Hepatic mTORC1 controls locomotor activity, body temperature, and lipid metabolism through FGF21.

    PubMed

    Cornu, Marion; Oppliger, Wolfgang; Albert, Verena; Robitaille, Aaron M; Trapani, Francesca; Quagliata, Luca; Fuhrer, Tobias; Sauer, Uwe; Terracciano, Luigi; Hall, Michael N

    2014-08-12

    The liver is a key metabolic organ that controls whole-body physiology in response to nutrient availability. Mammalian target of rapamycin (mTOR) is a nutrient-activated kinase and central controller of growth and metabolism that is negatively regulated by the tumor suppressor tuberous sclerosis complex 1 (TSC1). To investigate the role of hepatic mTOR complex 1 (mTORC1) in whole-body physiology, we generated liver-specific Tsc1 (L-Tsc1 KO) knockout mice. L-Tsc1 KO mice displayed reduced locomotor activity, body temperature, and hepatic triglyceride content in a rapamycin-sensitive manner. Ectopic activation of mTORC1 also caused depletion of hepatic and plasma glutamine, leading to peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α)-dependent fibroblast growth factor 21 (FGF21) expression in the liver. Injection of glutamine or knockdown of PGC-1α or FGF21 in the liver suppressed the behavioral and metabolic defects due to mTORC1 activation. Thus, mTORC1 in the liver controls whole-body physiology through PGC-1α and FGF21. Finally, mTORC1 signaling correlated with FGF21 expression in human liver tumors, suggesting that treatment of glutamine-addicted cancers with mTOR inhibitors might have beneficial effects at both the tumor and whole-body level.

  6. Chronic Social Stress in Puberty Alters Appetitive Male Sexual Behavior and Neural Metabolic Activity

    PubMed Central

    Bastida, Christel C.; Puga, Frank; Gonzalez-Lima, Francisco; Jennings, Kimberly J.; Wommack, Joel C.; Delville, Yvon

    2014-01-01

    Repeated social subjugation in early puberty lowers testosterone levels. We used hamsters to investigate the effects of social subjugation on male sexual behavior and metabolic activity within neural systems controlling social and motivational behaviors. Subjugated animals were exposed daily to aggressive adult males in early puberty for postnatal days 28 to 42, while control animals were placed in empty clean cages. On postnatal day 45, they were tested for male sexual behavior in the presence of receptive female. Alternatively, they were tested for mate choice after placement at the base of a Y-maze containing a sexually receptive female in one tip of the maze and an ovariectomized one on the other. Social subjugation did not affect the capacity to mate with receptive females. Although control animals were fast to approach females and preferred ovariectomized individuals, subjugated animals stayed away from them and showed no preference. Cytochrome oxidase activity was reduced within the preoptic area and ventral tegmental area in subjugated hamsters. In addition, the correlation of metabolic activity of these areas with the bed nucleus of the stria terminalis and anterior parietal cortex changed significantly from positive in controls to negative in subjugated animals. These data show that at mid-puberty, while male hamsters are capable of mating, their appetitive sexual behavior is not fully mature and this aspect of male sexual behavior is responsive to social subjugation. Furthermore, metabolic activity and coordination of activity in brain areas related to sexual behavior and motivation was altered by social subjugation. PMID:24852486

  7. Effects of sublethal dose of fipronil on neuron metabolic activity of Africanized honeybees.

    PubMed

    Roat, Thaisa Cristina; Carvalho, Stephan M; Nocelli, Roberta C F; Silva-Zacarin, Elaine C M; Palma, Mario Sérgio; Malaspina, Osmar

    2013-04-01

    Fipronil is a neurotoxic insecticide that inhibits the gamma-aminobutyric acid receptor and can affect gustative perception, olfactory learning, and motor activity of the honeybee Apis mellifera. This study determined the lethal dose (LD50) and the lethal concentration (LC50) for Africanized honeybee and evaluated the toxicity of a sublethal dose of fipronil on neuron metabolic activity by way of histochemical analysis using cytochrome oxidase detection in brains from worker bees of different ages. In addition, the present study investigated the recovery mechanism by discontinuing the oral exposure to fipronil. The results showed that mushroom bodies of aged Africanized honeybees are affected by fipronil, which causes changes in metabolism by increasing the respiratory activity of mitochondria. In antennal lobes, the sublethal dose of fipronil did not cause an increase in metabolic activity. The recovery experiments showed that discontinued exposure to a diet contaminated with fipronil did not lead to recovery of neural activity. Our results show that even at very low concentrations, fipronil is harmful to honeybees and can induce several types of injuries to honeybee physiology.

  8. Metabolic equivalents of task are confounded by adiposity, which disturbs objective measurement of physical activity.

    PubMed

    Tompuri, Tuomo T

    2015-01-01

    Physical activity refers any bodily movements produced by skeletal muscles that expends energy. Hence the amount and the intensity of physical activity can be assessed by energy expenditure. Metabolic equivalents of task (MET) are multiplies of the resting metabolism reflecting metabolic rate during exercise. The standard MET is defined as 3.5 ml/min/kg. However, the expression of energy expenditure by body weight to normalize the size differences between subjects causes analytical hazards: scaling by body weight does not have a physiological, mathematical, or physical rationale. This review demonstrates by examples that false methodology may cause paradoxical observations if physical activity would be assessed by body weight scaled values such as standard METs. While standard METs are confounded by adiposity, lean mass proportional measures of energy expenditure would enable a more truthful choice to assess physical activity. While physical activity as a behavior and cardiorespiratory fitness or adiposity as a state represents major determinants of public health, specific measurements of health determinants must be understood to enable a truthful evaluation of the interactions and their independent role as a health predictor.

  9. Metabolic equivalents of task are confounded by adiposity, which disturbs objective measurement of physical activity

    PubMed Central

    Tompuri, Tuomo T.

    2015-01-01

    Physical activity refers any bodily movements produced by skeletal muscles that expends energy. Hence the amount and the intensity of physical activity can be assessed by energy expenditure. Metabolic equivalents of task (MET) are multiplies of the resting metabolism reflecting metabolic rate during exercise. The standard MET is defined as 3.5 ml/min/kg. However, the expression of energy expenditure by body weight to normalize the size differences between subjects causes analytical hazards: scaling by body weight does not have a physiological, mathematical, or physical rationale. This review demonstrates by examples that false methodology may cause paradoxical observations if physical activity would be assessed by body weight scaled values such as standard METs. While standard METs are confounded by adiposity, lean mass proportional measures of energy expenditure would enable a more truthful choice to assess physical activity. While physical activity as a behavior and cardiorespiratory fitness or adiposity as a state represents major determinants of public health, specific measurements of health determinants must be understood to enable a truthful evaluation of the interactions and their independent role as a health predictor. PMID:26321958

  10. Inhibition of O-GlcNAc transferase activity reprograms prostate cancer cell metabolism

    PubMed Central

    Itkonen, Harri M.; Gorad, Saurabh S.; Duveau, Damien Y.; Martin, Sara E.S.; Barkovskaya, Anna; Bathen, Tone F.; Moestue, Siver A.; Mills, Ian G.

    2016-01-01

    Metabolic networks are highly connected and complex, but a single enzyme, O-GlcNAc transferase (OGT) can sense the availability of metabolites and also modify target proteins. We show that inhibition of OGT activity inhibits the proliferation of prostate cancer cells, leads to sustained loss of c-MYC and suppresses the expression of CDK1, elevated expression of which predicts prostate cancer recurrence (p=0.00179). Metabolic profiling revealed decreased glucose consumption and lactate production after OGT inhibition. This decreased glycolytic activity specifically sensitized prostate cancer cells, but not cells representing normal prostate epithelium, to inhibitors of oxidative phosphorylation (rotenone and metformin). Intra-cellular alanine was depleted upon OGT inhibitor treatment. OGT inhibitor increased the expression and activity of alanine aminotransferase (GPT2), an enzyme that can be targeted with a clinically approved drug, cycloserine. Simultaneous inhibition of OGT and GPT2 inhibited cell viability and growth rate, and additionally activated a cell death response. These combinatorial effects were predominantly seen in prostate cancer cells, but not in a cell-line derived from normal prostate epithelium. Combinatorial treatments were confirmed with two inhibitors against both OGT and GPT2. Taken together, here we report the reprogramming of energy metabolism upon inhibition of OGT activity, and identify synergistically lethal combinations that are prostate cancer cell specific. PMID:26824323

  11. Physiological community ecology: variation in metabolic activity of ecologically important rocky intertidal invertebrates along environmental gradients.

    PubMed

    Dahlhoff, Elizabeth P; Stillman, Jonathon H; Menge, Bruce A

    2002-08-01

    Rocky intertidal invertebrates live in heterogeneous habitats characterized by steep gradients in wave activity, tidal flux, temperature, food quality and food availability. These environmental factors impact metabolic activity via changes in energy input and stress-induced alteration of energetic demands. For keystone species, small environmentally induced shifts in metabolic activity may lead to disproportionately large impacts on community structure via changes in growth or survival of these key species. Here we use biochemical indicators to assess how natural differences in wave exposure, temperature and food availability may affect metabolic activity of mussels, barnacles, whelks and sea stars living at rocky intertidal sites with different physical and oceanographic characteristics. We show that oxygen consumption rate is correlated with the activity of key metabolic enzymes (e.g., citrate synthase and malate dehydrogenase) for some intertidal species, and concentrations of these enzymes in certain tissues are lower for starved individuals than for those that are well fed. We also show that the ratio of RNA to DNA (an index of protein synthetic capacity) is highly variable in nature and correlates with short-term changes in food availability. We also observed striking patterns in enzyme activity and RNA/DNA in nature, which are related to differences in rocky intertidal community structure. Differences among species and habitats are most pronounced in summer and are linked to high nearshore productivity at sites favored by suspension feeders and to exposure to stressful low-tide air temperatures in areas of low wave splash. These studies illustrate the great promise of using biochemical indicators to test ecological models, which predict changes in community structure along environmental gradients. Our results also suggest that biochemical indices must be carefully validated with laboratory studies, so that the indicator selected is likely to respond to the

  12. Physiological community ecology: variation in metabolic activity of ecologically important rocky intertidal invertebrates along environmental gradients.

    PubMed

    Dahlhoff, Elizabeth P; Stillman, Jonathon H; Menge, Bruce A

    2002-08-01

    Rocky intertidal invertebrates live in heterogeneous habitats characterized by steep gradients in wave activity, tidal flux, temperature, food quality and food availability. These environmental factors impact metabolic activity via changes in energy input and stress-induced alteration of energetic demands. For keystone species, small environmentally induced shifts in metabolic activity may lead to disproportionately large impacts on community structure via changes in growth or survival of these key species. Here we use biochemical indicators to assess how natural differences in wave exposure, temperature and food availability may affect metabolic activity of mussels, barnacles, whelks and sea stars living at rocky intertidal sites with different physical and oceanographic characteristics. We show that oxygen consumption rate is correlated with the activity of key metabolic enzymes (e.g., citrate synthase and malate dehydrogenase) for some intertidal species, and concentrations of these enzymes in certain tissues are lower for starved individuals than for those that are well fed. We also show that the ratio of RNA to DNA (an index of protein synthetic capacity) is highly variable in nature and correlates with short-term changes in food availability. We also observed striking patterns in enzyme activity and RNA/DNA in nature, which are related to differences in rocky intertidal community structure. Differences among species and habitats are most pronounced in summer and are linked to high nearshore productivity at sites favored by suspension feeders and to exposure to stressful low-tide air temperatures in areas of low wave splash. These studies illustrate the great promise of using biochemical indicators to test ecological models, which predict changes in community structure along environmental gradients. Our results also suggest that biochemical indices must be carefully validated with laboratory studies, so that the indicator selected is likely to respond to the

  13. Xenobiotic metabolizing enzyme activities in cells used for testing skin sensitization in vitro.

    PubMed

    Fabian, E; Vogel, D; Blatz, V; Ramirez, T; Kolle, S; Eltze, T; van Ravenzwaay, B; Oesch, F; Landsiedel, R

    2013-09-01

    For ethical and regulatory reasons, in vitro tests for scoring potential toxicities of cosmetics are essential. A test strategy for investigating potential skin sensitization using two human keratinocytic and two human dendritic cell lines has been developed (Mehling et al. Arch Toxicol 86:1273–1295, 2012). Since prohaptens may be metabolically activated in the skin, information on xenobiotic metabolizing enzyme (XME) activities in these cell lines is of high interest. In this study, XME activity assays, monitoring metabolite or cofactor, showed the following: all three passages of keratinocytic (KeratinoSens® and LuSens) and dendritic (U937 und THP-1) cells displayed N-acetyltransferase 1 (NAT1) activities (about 6–60 nmol/min/mg S9-protein for acetylation of para-aminobenzoic acid). This is relevant since reactive species of many cosmetics are metabolically controlled by cutaneous NAT1. Esterase activities of about 1–4 nmol fluorescein diacetate/min/mg S9-protein were observed in all passages of investigated keratinocytic and about 1 nmol fluorescein diacetate/min/mg S9-protein in dendritic cell lines. This is also of practical relevance since many esters and amides are detoxified and others activated by cutaneous esterases. In both keratinocytic cell lines, activities of aldehyde dehydrogenase (ALDH) were observed (5–17 nmol product/min/mg cytosolic protein). ALDH is relevant for the detoxication of reactive aldehydes. Activities of several other XME were below detection, namely the investigated cytochrome P450-dependent alkylresorufin O-dealkylases 7-ethylresorufin O-deethylase, 7-benzylresorufin O-debenzylase and 7-pentylresorufin O-depentylase (while NADPH cytochrome c reductase activities were much above the limit of quantification), the flavin-containing monooxygenase, the alcohol dehydrogenase as well as the UDP glucuronosyl transferase activities.

  14. Metabolic activity and behavior of the invasive amphipod Dikerogammarus villosus and two common Central European gammarid species (Gammarus fossarum, Gammarus roeselii): Low metabolic rates may favor the invader.

    PubMed

    Becker, Jochen; Ortmann, Christian; Wetzel, Markus A; Koop, Jochen H E

    2016-01-01

    The Ponto-Caspian amphipod Dikerogammarus villosus is one of the most successful invaders in Central European rivers. Contrary to studies on its ecology, ecophysiological studies comparing the species' physiological traits are scarce. In this context, in particular the metabolic activity of the invasive species has rarely been considered and, moreover, the few existing studies on this species report strongly deviating results. The purpose of this study was to assess the metabolic activity and behavior of D. villosus and other common European amphipod species (Gammarus fossarum, Gammarus roeselii) in relation to temperatures covering the thermal regime of the invaded habitats. Based on direct calorimetric measurements of metabolic heat dissipation at three temperature levels (5°C, 15°C and 25°C), we found the routine metabolic rate of D. villosus to be significantly lower than that of the other studied gammarid species at the medium temperature level. The estimated resting metabolic rate indicated a similar trend. At 5°C and 25°C, both routine and resting metabolic rate did not differ between species. Compared to G. fossarum and G. roeselii, D. villosus exhibited lower locomotor activity at the low and medium temperatures (5°C and 15°C). In contrast, its locomotor activity increased at the high experimental temperature (25°C). G. fossarum and G. roeselii were apparently more active than D. villosus at all studied temperatures. We conclude that D. villosus has both physiological and behavioral adaptations that lead to a reduction in metabolic energy expenditure, which is assumed to be beneficial and might contribute to its invasive success.

  15. Low resting metabolic rate in exercise-associated amenorrhea is not due to a reduced proportion of highly active metabolic tissue compartments.

    PubMed

    Koehler, Karsten; Williams, Nancy I; Mallinson, Rebecca J; Southmayd, Emily A; Allaway, Heather C M; De Souza, Mary Jane

    2016-08-01

    Exercising women with menstrual disturbances frequently display a low resting metabolic rate (RMR) when RMR is expressed relative to body size or lean mass. However, normalizing RMR for body size or lean mass does not account for potential differences in the size of tissue compartments with varying metabolic activities. To explore whether the apparent RMR suppression in women with exercise-associated amenorrhea is a consequence of a lower proportion of highly active metabolic tissue compartments or the result of metabolic adaptations related to energy conservation at the tissue level, RMR and metabolic tissue compartments were compared among exercising women with amenorrhea (AMEN; n = 42) and exercising women with eumenorrheic, ovulatory menstrual cycles (OV; n = 37). RMR was measured using indirect calorimetry and predicted from the size of metabolic tissue compartments as measured by dual-energy X-ray absorptiometry (DEXA). Measured RMR was lower than DEXA-predicted RMR in AMEN (1,215 ± 31 vs. 1,327 ± 18 kcal/day, P < 0.001) but not in OV (1,284 ± 24 vs. 1,252 ± 17, P = 0.16), resulting in a lower ratio of measured to DEXA-predicted RMR in AMEN (91 ± 2%) vs. OV (103 ± 2%, P < 0.001). AMEN displayed proportionally more residual mass (P < 0.001) and less adipose tissue (P = 0.003) compared with OV. A lower ratio of measured to DXA-predicted RMR was associated with lower serum total triiodothyronine (ρ = 0.38, P < 0.001) and leptin (ρ = 0.32, P = 0.004). Our findings suggest that RMR suppression in this population is not the result of a reduced size of highly active metabolic tissue compartments but is due to metabolic and endocrine adaptations at the tissue level that are indicative of energy conservation.

  16. Low resting metabolic rate in exercise-associated amenorrhea is not due to a reduced proportion of highly active metabolic tissue compartments.

    PubMed

    Koehler, Karsten; Williams, Nancy I; Mallinson, Rebecca J; Southmayd, Emily A; Allaway, Heather C M; De Souza, Mary Jane

    2016-08-01

    Exercising women with menstrual disturbances frequently display a low resting metabolic rate (RMR) when RMR is expressed relative to body size or lean mass. However, normalizing RMR for body size or lean mass does not account for potential differences in the size of tissue compartments with varying metabolic activities. To explore whether the apparent RMR suppression in women with exercise-associated amenorrhea is a consequence of a lower proportion of highly active metabolic tissue compartments or the result of metabolic adaptations related to energy conservation at the tissue level, RMR and metabolic tissue compartments were compared among exercising women with amenorrhea (AMEN; n = 42) and exercising women with eumenorrheic, ovulatory menstrual cycles (OV; n = 37). RMR was measured using indirect calorimetry and predicted from the size of metabolic tissue compartments as measured by dual-energy X-ray absorptiometry (DEXA). Measured RMR was lower than DEXA-predicted RMR in AMEN (1,215 ± 31 vs. 1,327 ± 18 kcal/day, P < 0.001) but not in OV (1,284 ± 24 vs. 1,252 ± 17, P = 0.16), resulting in a lower ratio of measured to DEXA-predicted RMR in AMEN (91 ± 2%) vs. OV (103 ± 2%, P < 0.001). AMEN displayed proportionally more residual mass (P < 0.001) and less adipose tissue (P = 0.003) compared with OV. A lower ratio of measured to DXA-predicted RMR was associated with lower serum total triiodothyronine (ρ = 0.38, P < 0.001) and leptin (ρ = 0.32, P = 0.004). Our findings suggest that RMR suppression in this population is not the result of a reduced size of highly active metabolic tissue compartments but is due to metabolic and endocrine adaptations at the tissue level that are indicative of energy conservation. PMID:27382033

  17. Altered metabolism of gut microbiota contributes to chronic immune activation in HIV-infected individuals.

    PubMed

    Vázquez-Castellanos, J F; Serrano-Villar, S; Latorre, A; Artacho, A; Ferrús, M L; Madrid, N; Vallejo, A; Sainz, T; Martínez-Botas, J; Ferrando-Martínez, S; Vera, M; Dronda, F; Leal, M; Del Romero, J; Moreno, S; Estrada, V; Gosalbes, M J; Moya, A

    2015-07-01

    Altered interplay between gut mucosa and microbiota during treated HIV infection may possibly contribute to increased bacterial translocation and chronic immune activation, both of which are predictors of morbidity and mortality. Although a dysbiotic gut microbiota has recently been reported in HIV+ individuals, the metagenome gene pool associated with HIV infection remains unknown. The aim of this study is to characterize the functional gene content of gut microbiota in HIV+ patients and to define the metabolic pathways of this bacterial community, which is potentially associated with immune dysfunction. We determined systemic markers of innate and adaptive immunity in a cohort of HIV-infected individuals on successful antiretroviral therapy without comorbidities and in healthy non-HIV-infected subjects. Metagenome sequencing revealed an altered functional profile, with enrichment of the genes involved in various pathogenic processes, lipopolysaccharide biosynthesis, bacterial translocation, and other inflammatory pathways. In contrast, we observed depletion of genes involved in amino acid metabolism and energy processes. Bayesian networks showed significant interactions between the bacterial community, their altered metabolic pathways, and systemic markers of immune dysfunction. This study reveals altered metabolic activity of microbiota and provides novel insight into the potential host-microbiota interactions driving the sustained inflammatory state in successfully treated HIV-infected patients. PMID:25407519

  18. Altered metabolism of gut microbiota contributes to chronic immune activation in HIV-infected individuals.

    PubMed

    Vázquez-Castellanos, J F; Serrano-Villar, S; Latorre, A; Artacho, A; Ferrús, M L; Madrid, N; Vallejo, A; Sainz, T; Martínez-Botas, J; Ferrando-Martínez, S; Vera, M; Dronda, F; Leal, M; Del Romero, J; Moreno, S; Estrada, V; Gosalbes, M J; Moya, A

    2015-07-01

    Altered interplay between gut mucosa and microbiota during treated HIV infection may possibly contribute to increased bacterial translocation and chronic immune activation, both of which are predictors of morbidity and mortality. Although a dysbiotic gut microbiota has recently been reported in HIV+ individuals, the metagenome gene pool associated with HIV infection remains unknown. The aim of this study is to characterize the functional gene content of gut microbiota in HIV+ patients and to define the metabolic pathways of this bacterial community, which is potentially associated with immune dysfunction. We determined systemic markers of innate and adaptive immunity in a cohort of HIV-infected individuals on successful antiretroviral therapy without comorbidities and in healthy non-HIV-infected subjects. Metagenome sequencing revealed an altered functional profile, with enrichment of the genes involved in various pathogenic processes, lipopolysaccharide biosynthesis, bacterial translocation, and other inflammatory pathways. In contrast, we observed depletion of genes involved in amino acid metabolism and energy processes. Bayesian networks showed significant interactions between the bacterial community, their altered metabolic pathways, and systemic markers of immune dysfunction. This study reveals altered metabolic activity of microbiota and provides novel insight into the potential host-microbiota interactions driving the sustained inflammatory state in successfully treated HIV-infected patients.

  19. Role of peroxisome proliferator-activated receptors gene polymorphisms in type 2 diabetes and metabolic syndrome

    PubMed Central

    Dong, Chen; Zhou, Hui; Shen, Chong; Yu, Lu-Gang; Ding, Yi; Zhang, Yong-Hong; Guo, Zhi-Rong

    2015-01-01

    Metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) are the serious public health problems worldwide. Moreover, it is estimated that MetS patients have about five-fold greater risk of the T2DM development compared with people without the syndrome. Peroxisome proliferator-activated receptors are a subgroup of the nuclear hormone receptor superfamily of ligand-activated transcription factors which play an important role in the pathogenesis of MetS and T2DM. All three members of the peroxisome proliferator-activated receptor (PPAR) nuclear receptor subfamily, PPARα, PPARβ/δ and PPARγ are critical in regulating insulin sensitivity, adipogenesis, lipid metabolism, and blood pressure. Recently, more and more studies indicated that the gene polymorphism of PPARs, such as Leu162Val and Val227Ala of PPARα, +294T > C of PPARβ/δ, Pro12Ala and C1431T of PPARγ, are significantly associated with the onset and progressing of MetS and T2DM in different population worldwide. Furthermore, a large body of evidence demonstrated that the glucose metabolism and lipid metabolism were influenced by gene-gene interaction among PPARs genes. However, given the complexity pathogenesis of metabolic disease, it is unlikely that genetic variation of a single locus would provide an adequate explanation of inter-individual differences which results in diverse clinical syndromes. Thus, gene-gene interactions and gene-environment interactions associated with T2DM and MetS need future comprehensive studies. PMID:25987964

  20. Seasonal variation in metabolic rate, flight activity and body size of Anopheles gambiae in the Sahel

    PubMed Central

    Huestis, Diana L.; Yaro, Alpha S.; Traoré, Adama I.; Dieter, Kathryne L.; Nwagbara, Juliette I.; Bowie, Aleah C.; Adamou, Abdoulaye; Kassogué, Yaya; Diallo, Moussa; Timbiné, Seydou; Dao, Adama; Lehmann, Tovi

    2012-01-01

    SUMMARY Malaria in Africa is vectored primarily by the Anopheles gambiae complex. Although the mechanisms of population persistence during the dry season are not yet known, targeting dry season mosquitoes could provide opportunities for vector control. In the Sahel, it appears likely that M-form A. gambiae survive by aestivation (entering a dormant state). To assess the role of eco-physiological changes associated with dry season survival, we measured body size, flight activity and metabolic rate of wild-caught mosquitoes throughout 1 year in a Sahelian locality, far from permanent water sources, and at a riparian location adjacent to the Niger River. We found significant seasonal variation in body size at both the Sahelian and riparian sites, although the magnitude of the variation was greater in the Sahel. For flight activity, significant seasonality was only observed in the Sahel, with increased flight activity in the wet season when compared with that just prior to and throughout the dry season. Whole-organism metabolic rate was affected by numerous biotic and abiotic factors, and a significant seasonal component was found at both locations. However, assay temperature accounted completely for seasonality at the riparian location, while significant seasonal variation remained after accounting for all measured variables in the Sahel. Interestingly, we did not find that mean metabolic rate was lowest during the dry season at either location, contrary to our expectation that mosquitoes would conserve energy and increase longevity by reducing metabolism during this time. These results indicate that mosquitoes may use mechanisms besides reduced metabolic rate to enable survival during the Sahelian dry season. PMID:22623189

  1. DMPP-added nitrogen fertilizer affects soil N2O emission and microbial activity in Southern Italy

    NASA Astrophysics Data System (ADS)

    Vitale, Luca; De Marco, Anna; Maglione, Giuseppe; Polimeno, Franca; Di Tommasi, Paul; Magliulo, Vincenzo

    2014-05-01

    Arable sites contributes to global N2O emission due to massive utilization of nitrogen fertilizers. N2O derives from the biological processes such as nitrification and denitrification influenced by soil nitrogen availability. The use of nitrogen fertilizers added with nitrification inhibitors represents one among the proposed strategy to reduce soil N2O emission form arable sites. The aim of this work was to evaluate the effects of 3,4-dimethylphyrazole phosphate (DMPP), a nitrification inhibitor, on N2O emission and microbial activity of a soil cropped to potato in Southern Italy. The experiment was a randomized block design with two treatments applied and three replicates: control (C) and DMPP (Entec®, K+S Nitrogen) plots, both supplied with the same amount of ammonium nitrate. The nitrogen fertilizer was supplied in three events: at 0 Day After Sowing (DAS; 100 kg N ha-1), at 57 DAS (30 kg N ha-1), and at 71 DAS (30 kg N ha-1). Soil N2O emission was monitored by both dynamic and static chambers. Static chambers were located both on hills and furrows whereas dynamic chambers were located on furrows. Air samples were collected from chambers at different times and analysed by a gas chromatograph (SRI 8610C, Gas Chromatograph). Fluxes were estimated as a linear interpolation of N2O changes over a 30 min time. Microbial biomass and basal respiration were determined as CO2 evolution, analysed by means of an IRGA (Li6200, Licor), on 2 g of fresh soil over a 4h incubation time. Microbial biomass was determined by Substrate Induced Respiration method. Data show no statistical differences in N2O fluxes measured with either dynamic chambers between C and DMPP plots in studied period. However, after the first fertilization event, when the fertilizer was applied as 100 kg N ha-1, the average N2O fluxes measured with static chambers were higher in DMPP plots compared to C plots. In the same period, the microbial biomass significantly decreased in DMPP plots as compared to C

  2. Human aldo-keto reductases and the metabolic activation of polycyclic aromatic hydrocarbons.

    PubMed

    Penning, Trevor M

    2014-11-17

    Aldo-keto reductases (AKRs) are promiscuous NAD(P)(H) dependent oxidoreductases implicated in the metabolic activation of polycyclic aromatic hydrocarbons (PAH). These enzymes catalyze the oxidation of non-K-region trans-dihydrodiols to the corresponding o-quinones with the concomitant production of reactive oxygen species (ROS). The PAH o-quinones are Michael acceptors and can form adducts but are also redox-active and enter into futile redox cycles to amplify ROS formation. Evidence exists to support this metabolic pathway in humans. The human recombinant AKR1A1 and AKR1C1-AKR1C4 enzymes all catalyze the oxidation of PAH trans-dihydrodiols to PAH o-quinones. Many human AKRs also catalyze the NADPH-dependent reduction of the o-quinone products to air-sensitive catechols, exacerbating ROS formation. Moreover, this pathway of PAH activation occurs in a panel of human lung cell lines, resulting in the production of ROS and oxidative DNA damage in the form of 8-oxo-2'-deoxyguanosine. Using stable-isotope dilution liquid chromatography tandem mass spectrometry, this pathway of benzo[a]pyrene (B[a]P) metabolism was found to contribute equally with the diol-epoxide pathway to the activation of this human carcinogen in human lung cells. Evaluation of the mutagenicity of anti-B[a]P-diol epoxide with B[a]P-7,8-dione on p53 showed that the o-quinone produced by AKRs was the more potent mutagen, provided that it was permitted to redox cycle, and that the mutations observed were G to T transversions, reminiscent of those observed in human lung cancer. It is concluded that there is sufficient evidence to support the role of human AKRs in the metabolic activation of PAH in human lung cell lines and that they may contribute to the causation of human lung cancer.

  3. Human Aldo-Keto Reductases and the Metabolic Activation of Polycyclic Aromatic Hydrocarbons

    PubMed Central

    2015-01-01

    Aldo-keto reductases (AKRs) are promiscuous NAD(P)(H) dependent oxidoreductases implicated in the metabolic activation of polycyclic aromatic hydrocarbons (PAH). These enzymes catalyze the oxidation of non-K-region trans-dihydrodiols to the corresponding o-quinones with the concomitant production of reactive oxygen species (ROS). The PAH o-quinones are Michael acceptors and can form adducts but are also redox-active and enter into futile redox cycles to amplify ROS formation. Evidence exists to support this metabolic pathway in humans. The human recombinant AKR1A1 and AKR1C1–AKR1C4 enzymes all catalyze the oxidation of PAH trans-dihydrodiols to PAH o-quinones. Many human AKRs also catalyze the NADPH-dependent reduction of the o-quinone products to air-sensitive catechols, exacerbating ROS formation. Moreover, this pathway of PAH activation occurs in a panel of human lung cell lines, resulting in the production of ROS and oxidative DNA damage in the form of 8-oxo-2′-deoxyguanosine. Using stable-isotope dilution liquid chromatography tandem mass spectrometry, this pathway of benzo[a]pyrene (B[a]P) metabolism was found to contribute equally with the diol-epoxide pathway to the activation of this human carcinogen in human lung cells. Evaluation of the mutagenicity of anti-B[a]P-diol epoxide with B[a]P-7,8-dione on p53 showed that the o-quinone produced by AKRs was the more potent mutagen, provided that it was permitted to redox cycle, and that the mutations observed were G to T transversions, reminiscent of those observed in human lung cancer. It is concluded that there is sufficient evidence to support the role of human AKRs in the metabolic activation of PAH in human lung cell lines and that they may contribute to the causation of human lung cancer. PMID:25279998

  4. Reactive Oxygen Species in the Paraventricular Nucleus of the Hypothalamus Alter Sympathetic Activity During Metabolic Syndrome.

    PubMed

    Cruz, Josiane C; Flôr, Atalia F L; França-Silva, Maria S; Balarini, Camille M; Braga, Valdir A

    2015-01-01

    The paraventricular nucleus of the hypothalamus (PVN) contains heterogeneous populations of neurons involved in autonomic and neuroendocrine regulation. The PVN plays an important role in the sympathoexcitatory response to increasing circulating levels of angiotensin II (Ang-II), which activates AT1 receptors in the circumventricular organs (OCVs), mainly in the subfornical organ (SFO). Circulating Ang-II induces a de novo synthesis of Ang-II in SFO neurons projecting to pre-autonomic PVN neurons. Activation of AT1 receptors induces intracellular increases in reactive oxygen species (ROS), leading to increases in sympathetic nerve activity (SNA). Chronic sympathetic nerve activation promotes a series of metabolic disorders that characterizes the metabolic syndrome (MetS): dyslipidemia, hyperinsulinemia, glucose intolerance, hyperleptinemia and elevated plasma hormone levels, such as noradrenaline, glucocorticoids, leptin, insulin, and Ang-II. This review will discuss the contribution of our laboratory and others regarding the sympathoexcitation caused by peripheral Ang-II-induced reactive oxygen species along the subfornical organ and paraventricular nucleus of the hypothalamus. We hypothesize that this mechanism could be involved in metabolic disorders underlying MetS. PMID:26779026

  5. A novel LKB1 isoform enhances AMPK metabolic activity and displays oncogenic properties.

    PubMed

    Dahmani, R; Just, P-A; Delay, A; Canal, F; Finzi, L; Prip-Buus, C; Lambert, M; Sujobert, P; Buchet-Poyau, K; Miller, E; Cavard, C; Marmier, S; Terris, B; Billaud, M; Perret, C

    2015-04-30

    The LKB1 tumor suppressor gene encodes a master kinase that coordinates the regulation of energetic metabolism and cell polarity. We now report the identification of a novel isoform of LKB1 (named ΔN-LKB1) that is generated through alternative transcription and internal initiation of translation of the LKB1 mRNA. The ΔN-LKB1 protein lacks the N-terminal region and a portion of the kinase domain. Although ΔN-LKB1 is catalytically inactive, it potentiates the stimulating effect of LKB1 on the AMP-activated protein kinase (AMPK) metabolic sensor through a direct interaction with the regulatory autoinhibitory domain of AMPK. In contrast, ΔN-LKB1 negatively interferes with the LKB1 polarizing activity. Finally, combining in vitro and in vivo approaches, we showed that ΔN-LKB1 has an intrinsic oncogenic property. ΔN-LKB1 is expressed solely in the lung cancer cell line, NCI-H460. Silencing of ΔN-LKB1 decreased the survival of NCI-H460 cells and inhibited their tumorigenicity when engrafted in nude mice. In conclusion, we have identified a novel LKB1 isoform that enhances the LKB1-controlled AMPK metabolic activity but inhibits LKB1-induced polarizing activity. Both the LKB1 tumor suppressor gene and the oncogene ΔN-LKB1 are expressed from the same locus and this may account for some of the paradoxical effects of LKB1 during tumorigenesis.

  6. Use of human hepatoma cells for in vitro metabolic activation of chemical mutagens/carcinogens.

    PubMed

    Natarajan, A T; Darroudi, F

    1991-09-01

    An established human hepatoma cell strain (Hep G2) was used in micronuclei (MN) and sister chromatid exchange (SCE) assays to evaluate the clastogenic potential of several indirectly-acting mutagenic carcinogens. Benzo[a]pyrene, cyclophosphamide, dimethyl nitrosamine, hexamethylphosphoramide, pyrene and safrole were selected for this study based on the positive and negative results reported with conventional in vitro assays employing rat liver S9 fraction for metabolic activation. Two directly-acting mutagens, methyl methanesulphonate and mitomycin C, were also included in this study. In this system, the human hepatoma cells act as the metabolic activation source as well as the target cell for DNA damage. The results obtained demonstrate that the Hep G2 cells are metabolically competent to activate different classes of mutagens into biologically active metabolites. The non-carcinogen pyrene did not induce any increase in the frequencies of MN and SCE in Hep G2 cells. Furthermore, a good correlation was found between positive and negative data obtained for the tested chemicals in this in vitro assay with literature data obtained in in vivo tests using rodents.

  7. The effect of aspartame on the activity of rat liver xenobiotic-metabolizing enzymes.

    PubMed

    Tutelyan, V A; Kravchenko, L V; Kuzmina, E E

    1990-01-01

    Male, Wistar rats were administered aspartame (40 or 4000 mg/kg body weight) in their diet for 90 days. By 45 days, the activities of three microsomal enzymes, epoxide hydrolase, carboxylesterase, and p-nitrophenyl-UDP-glucuronosyltransferase, were significantly increased in rats consuming 4000 mg/kg of aspartame. By 90 days, however, the activity of the xenobiotic-metabolizing enzymes of the rats given aspartame did not differ significantly from the activity of control animals. From these results, we conclude that the consumption of aspartame does not substantially alter the function of the hepatic microsomal enzymes which protect the organism from foreign compounds found in its environment and food.

  8. Activation of AMPKα2 is not crucial for mitochondrial uncoupling-induced metabolic effects but required to maintain skeletal muscle integrity.

    PubMed

    Ost, Mario; Werner, Franziska; Dokas, Janine; Klaus, Susanne; Voigt, Anja

    2014-01-01

    Transgenic (UCP1-TG) mice with ectopic expression of UCP1 in skeletal muscle (SM) show a phenotype of increased energy expenditure, improved glucose tolerance and increase substrate metabolism in SM. To investigate the potential role of skeletal muscle AMPKα2 activation in the metabolic phenotype of UCP1-TG mice we generated double transgenic (DTG) mice, by crossing of UCP1-TG mice with DN-AMPKα2 mice overexpressing a dominant negative α2 subunit of AMPK in SM which resulted in an impaired AMPKα2 activity by 90±9% in SM of DTG mice. Biometric analysis of young male mice showed decreased body weight, lean and fat mass for both UCP1-TG and DTG compared to WT and DN-AMPKα2 mice. Energy intake and weight-specific total energy expenditure were increased, both in UCP1-TG and DTG mice. Moreover, glucose tolerance, insulin sensitivity and fatty acid oxidation were not altered in DTG compared to UCP1-TG. Also uncoupling induced induction and secretion of fibroblast growth factor 21 (FGF21) from SM was preserved in DTG mice. However, voluntary physical cage activity as well as ad libitum running wheel access during night uncovered a severe activity intolerance of DTG mice. Histological analysis showed a progressive degenerative morphology in SM of DTG mice which was not observed in SM of UCP1-TG mice. Moreover, ATP-depletion related cellular stress response via heat shock protein 70 was highly induced, whereas capillarization regulator VEGF was suppressed in DTG muscle. In addition, AMPKα2-mediated induction of mitophagy regulator ULK1 was suppressed in DTG mice, as well as mitochondrial respiratory capacity and content. In conclusion, we demonstrate that AMPKα2 is dispensable for SM mitochondrial uncoupling induced metabolic effects on whole body energy balance, glucose homeostasis and insulin sensitivity. But strikingly, activation of AMPKα2 seems crucial for maintaining SM function, integrity and the ability to compensate chronic metabolic stress induced by SM

  9. Chromospherically active stars. 12: ADS 11060 C: A double lined K dwarf binary in a quintuple system

    NASA Technical Reports Server (NTRS)

    Fekel, Francis C.; Henry, Gregory W.; Hampton, Melissa L.; Fried, Robert; Morton, Mary D.

    1994-01-01

    ADS 11060 C is a double lined spectroscopic binary with a period of 25.7631 days and an eccentricity of 0.565. Spectral types of the two stars are estimated as K7 V and MO V with a magnitude difference of about 0.55 mag in V. The stars appear to be somewhat metal rich with respect to the Sun. Despite the relatively large masses of 0.53 and 0.51 solar mass, our photometric observations find no evidence for eclipses and we estimate an inclination of 77 deg plus or minus 11 deg. ADS 11060 C is, however, photometrically variable with a period of 9 plus or minus 1 day and an amplitude of 0.05 mag in V. Thus, it is a newly identified BY Draconis variable. The center-of-mass velocity of ADS 11060 C and an estimated parallax of 0.030 sec support its physical association with ADS 11060 AB, making this a quintuple system. The projected separation of the AB-C system is nearly 1200 AU. Although the log lithium abundances of the two components of ADS 11060 C are only upper limits, less than or equal to -0.14, lithium abundances of the AB-C components appear to be consistent with those of similar stars in the alpha Persei and Pleiades clusters, suggesting an age of about 70 Myr for ADS 11060 AB-C. The system is a possible member of the Pleiades moving group. Listed as an optical counterpart to a source in the ROSAT Wide Field Camera extreme-ultraviolet bright source catalog, both ADS 11060 AB and C may contribute to the observed flux.

  10. Metabolic Activation of Rhein: Insights into the Potential Toxicity Induced by Rhein-Containing Herbs.

    PubMed

    Yuan, Yuan; Zheng, Jiyue; Wang, Meiyu; Li, Yuan; Ruan, Jianqing; Zhang, Hongjian

    2016-07-20

    Rhein is a major component of the many medicinal herbs such as rhubarb. Despite wide use, intoxication cases associated with rhein-containing herbs are often reported. The present work aimed to investigate if rhein was subject to metabolic activation leading to toxicity. Upon incubations with different species of liver microsomes, three monoglucuronides were identified, corresponding to two hydroxyl glucuronides and one acyl glucuronide via the carboxyl group, respectively. Further study revealed that rhein acyl glucuronide was chemically reactive, and showed cytotoxicity toward hepatocarcinoma cells. In addition, significant species differences in glucuronidation of rhein were observed between laboratory animals and humans. Reaction phenotyping experiments demonstrated that rhein acyl glucuronide was catalyzed predominantly by uridine 5'-diphospho-glucuronosyltransferase 1A1, 1A9, and 2B7. Taken together, the present study confirmed that rhein could be metabolically activated via the formation of acyl glucuronide, especially in human. PMID:27362917

  11. Direct neuronal glucose uptake heralds activity-dependent increases in cerebral metabolism

    PubMed Central

    Lundgaard, Iben; Li, Baoman; Xie, Lulu; Kang, Hongyi; Sanggaard, Simon; Haswell, John Douglas R; Sun, Wei; Goldman, Siri; Blekot, Solomiya; Nielsen, Michael; Takano, Takahiro; Deane, Rashid; Nedergaard, Maiken

    2015-01-01

    Metabolically, the brain is a highly active organ that relies almost exclusively on glucose as its energy source. According to the astrocyte-to-neuron lactate shuttle hypothesis, glucose is taken up by astrocytes and converted to lactate, which is then oxidized by neurons. Here we show, using 2-photon imaging of a near-infrared 2-deoxyglucose analogue (2DG-IR), that glucose is taken up preferentially by neurons in awake behaving mice. Anesthesia suppressed neuronal 2DG-IR uptake and sensory stimulation was associated with a sharp increase in neuronal, but not astrocytic, 2DG-IR uptake. Moreover, hexokinase, which catalyze the first enzymatic steps in glycolysis, was highly enriched in neurons compared with astrocytes, in mouse as well as in human cortex. These observations suggest that brain activity and neuronal glucose metabolism are directly linked, and identifies the neuron as the principal locus of glucose uptake as visualized by functional brain imaging. PMID:25904018

  12. [Detection of viable metabolically active yeast cells using a colorimetric assay].

    PubMed

    Růzicka, F; Holá, V

    2008-02-01

    The increasing concern of yeasts able to form biofilm brings about the need for susceptibility testing of both planktonic and biofilm cells. Detection of viability or metabolic activity of yeast cells after exposure to antimicrobials plays a key role in the assessment of susceptibility testing results. Colorimetric assays based on the color change of the medium in the presence of metabolically active cells proved suitable for this purpose. In this study, the usability of a colorimetric assay with the resazurin redox indicator for monitoring the effect of yeast inoculum density on the reduction rate was tested. As correlation between the color change rate and inoculum density was observed, approximate quantification of viable cells was possible. The assay would be of relevance to antifungal susceptibility testing in both planktonic and biofilm yeasts.

  13. Orbital fluid shear stress promotes osteoblast metabolism, proliferation and alkaline phosphates activity in vitro

    SciTech Connect

    Aisha, M.D.; Nor-Ashikin, M.N.K.; Sharaniza, A.B.R.; Nawawi, H.; Froemming, G.R.A.

    2015-09-10

    Prolonged disuse of the musculoskeletal system is associated with reduced mechanical loading and lack of anabolic stimulus. As a form of mechanical signal, the multidirectional orbital fluid shear stress transmits anabolic signal to bone forming cells in promoting cell differentiation, metabolism and proliferation. Signals are channeled through the cytoskeleton framework, directly modifying gene and protein expression. For that reason, we aimed to study the organization of Normal Human Osteoblast (NHOst) cytoskeleton with regards to orbital fluid shear (OFS) stress. Of special interest were the consequences of cytoskeletal reorganization on NHOst metabolism, proliferation, and osteogenic functional markers. Cells stimulated at 250 RPM in a shaking incubator resulted in the rearrangement of actin and tubulin fibers after 72 h. Orbital shear stress increased NHOst mitochondrial metabolism and proliferation, simultaneously preventing apoptosis. The ratio of RANKL/OPG was reduced, suggesting that orbital shear stress has the potential to inhibit osteoclastogenesis and osteoclast activity. Increase in ALP activity and OCN protein production suggests that stimulation retained osteoblast function. Shear stress possibly generated through actin seemed to hold an anabolic response as osteoblast metabolism and functional markers were enhanced. We hypothesize that by applying orbital shear stress with suitable magnitude and duration as a non-drug anabolic treatment can help improve bone regeneration in prolonged disuse cases. - Highlights: • OFS stress transmits anabolic signals to osteoblasts. • Actin and tubulin fibers are rearranged under OFS stress. • OFS stress increases mitochondrial metabolism and proliferation. • Reduced RANKL/OPG ratio in response to OFS inhibits osteoclastogenesis. • OFS stress prevents apoptosis and stimulates ALP and OCN.

  14. The Relationship Between Diabetes, Metabolic Syndrome, and Platelet Activity as Measured by Mean Platelet Volume

    PubMed Central

    Shah, Binita; Sha, Daohang; Xie, Dawei; Mohler, Emile R.; Berger, Jeffrey S.

    2012-01-01

    OBJECTIVE The association between platelet activity, diabetes, and glucometabolic control is uncertain. We aim to investigate mean platelet volume (MPV), a marker of platelet size and platelet activity, with the prevalence of diabetes, metabolic syndrome, and degree of glycemic control. RESEARCH DESIGN AND METHODS This is a retrospective analysis of 13,021 participants in the National Health and Nutrition Examination Survey from 1999 to 2004. Prevalence of diabetes was defined as nonfasting glucose >200 mg/dL, fasting glucose ≥126 mg/dL, or treatment with hypoglycemic agents. Presence of metabolic syndrome was determined by the National Cholesterol Education Program Adult Treatment Panel III definition. Odds ratios and 95% CIs were estimated by logistic regression. RESULTS MPV was significantly higher in subjects with diabetes (8.20 vs. 8.06 femtoliter [fL], P < 0.01) but not in subjects with metabolic syndrome (8.09 vs. 8.07 fL, P = 0.24). For the metabolic syndrome components, MPV was significantly higher in abdominal obesity (P = 0.03) and low HDL (P = 0.04), and not different in high blood pressure (P = 0.07), abnormal glucose metabolism (P = 0.71), or hypertriglyceridemia (P = 0.46). There was a significant correlation between MPV and glucose (P < 0.0001) and between MPV and hemoglobin A1c (P < 0.0001) in subjects with diabetes. These correlations were no longer significant in those without diabetes. The adjusted odds of diabetes rose with increasing MPV levels and were most pronounced in subjects with MPV levels exceeding the 90th percentile (≥9.31 fL). The association between MPV and diabetes was most apparent in those with the poorest glucose control. CONCLUSIONS Mean platelet volume is strongly and independently associated with the presence and severity of diabetes. PMID:22410814

  15. Tubulin polymerization by paclitaxel (taxol) phosphate prodrugs after metabolic activation with alkaline phosphatase.

    PubMed

    Mamber, S W; Mikkilineni, A B; Pack, E J; Rosser, M P; Wong, H; Ueda, Y; Forenza, S

    1995-08-01

    Paclitaxel (taxol) phosphate derivatives BMY46366, BMY-46489, BMS180661 and BMS180820 were used to determine the ability of alkaline phosphatase to convert these water-soluble potential prodrugs to tubulin-polymerizing metabolites (i.e., paclitaxel). Compounds were treated up to 180 min with an in vitro metabolic activation system composed of 10% bovine alkaline phosphatase in 0.2 M tris, pH 7.4, or in 0.2 M glycine, pH 8.8, plus 0.05 M MgCl2. Samples were tested (either by direct addition or after methylene chloride extraction/dimethyl-sulfoxide resuspension) in spectrophotometric tubulin polymerization assays utilizing bovine-derived microtubule protein. Pretreatment of 2'- and 7-phosphonoxyphenylpropionate prodrugs BMS180661 and BMS180820 with alkaline phosphatase for 30 to 120 min yielded relative initial slopes of about 20 to 100% at test concentrations equimolar to paclitaxel. High-performance liquid chromatography/mass spectrometry of BMS180661 treated with alkaline phosphatase confirmed the production of paclitaxel from the prodrug. In contrast, 2'- and 7-phosphate analogs BMY46366 and BMY46489 treated with alkaline phosphatase were not active in tubulin assays. None of the paclitaxel phosphate prodrugs polymerized tubulin in the absence of metabolic activation. The differences in tubulin polymerization with metabolic activation may be related both to accessibility of the phosphate group to the enzyme and to anionic charge effects. These results demonstrate that certain paclitaxel phosphate prodrugs can be metabolized by alkaline phosphatase to yield effective tubulin polymerization. PMID:7636751

  16. Lithogenic activity as a factor to consider in the metabolic evaluation of patients with calcium lithiasis.

    PubMed

    Arrabal-Polo, Miguel Angel; Cano-Garcia, Maria Del Carmen; Arrabal-Martin, Miguel

    2015-11-01

    Metabolic evaluation is important in high-risk patients with a history of urinary calculi, in order to prevent recurrence. This study aimed to compare patients with calcium calculi and mild lithogenic activity with those with moderate to severe lithogenic activity. Patients with moderate to severe activity had higher levels of urinary calcium level (271.9 mg/24h versus 172.1 mg/24 h, P < .001), uric acid (612.3 mg/24 h versus 528.9 mg/24h, P = .008), and fasting calcium-creatinine ratio (0.16 versus 0.12, P = .001) compared to those with mild lithogenic activity. No association was observed between lithogenic factors in 24-hour urine and mild lithogenic activity in multivariable analysis. We initially thought that in patients who develop recurrent calculi after 5 years or who have mild lithogenic activity, complete metabolic evaluation would not be necessary. However, based on our study findings, it may be important to conduct further studies assessing the lithogenic activity. PMID:26552354

  17. [Interaction between CYP450 enzymes and metabolism of traditional Chinese medicine as well as enzyme activity assay].

    PubMed

    Lu, Tu-lin; Su, Lian-lin; Ji, De; Gu, Wei; Mao, Chun-qin

    2015-09-01

    Drugs are exogenous compounds for human bodies, and will be metabolized by many enzymes after administration. CYP450 enzyme, as a major metabolic enzyme, is an important phase I drug metabolizing enzyme. In human bodies, about 75% of drug metabolism is conducted by CYP450 enzymes, and CYP450 enzymes is the key factor for drug interactions between traditional Chinese medicine( TCM) -TCM, TCM-medicine and other drug combination. In order to make clear the interaction between metabolic enzymes and TCM metabolism, we generally chose the enzymatic activity as an evaluation index. That is to say, the enhancement or reduction of CYP450 enzyme activity was used to infer the inducing or inhibitory effect of active ingredients and extracts of traditional Chinese medicine on enzymes. At present, the common method for measuring metabolic enzyme activity is Cocktail probe drugs, and it is the key to select the suitable probe substrates. This is of great significance for study drug's absorption, distribution, metabolism and excretion (ADME) process in organisms. The study focuses on the interaction between TCMs, active ingredients, herbal extracts, cocktail probe substrates as well as CYP450 enzymes, in order to guide future studies.

  18. Physical Activity and Sedentary Behavior in Metabolically Healthy versus Unhealthy Obese and Non-Obese Individuals – The Maastricht Study

    PubMed Central

    van der Berg, Julianne D.; van der Kallen, Carla J. H.; Schram, Miranda T.; Savelberg, Hans H. C. M.; Schaper, Nicolaas C.; Dagnelie, Pieter C.; Henry, Ronald M. A.; Kroon, Abraham A.; Stehouwer, Coen D. A.; Koster, Annemarie

    2016-01-01

    Background Both obesity and the metabolic syndrome are associated with increased risk of cardiovascular diseases and type 2 diabetes. Although both frequently occur together in the same individual, obesity and the metabolic syndrome can also develop independently from each other. The (patho)physiology of “metabolically healthy obese” (i.e. obese without metabolic syndrome) and “metabolically unhealthy non-obese” phenotypes (i.e. non-obese with metabolic syndrome) is not fully understood, but physical activity and sedentary behavior may play a role. Objective To examine objectively measured physical activity and sedentary behavior across four groups: I) “metabolically healthy obese” (MHO); II) “metabolically unhealthy obese” (MUO); III)”metabolically healthy non-obese” (MHNO); and IV) “metabolically unhealthy non-obese” (MUNO). Methods Data were available from 2,449 men and women aged 40–75 years who participated in The Maastricht Study from 2010 to 2013. Participants were classified into the four groups according to obesity (BMI≥30kg/m2) and metabolic syndrome (ATPIII definition). Daily activity was measured for 7 days with the activPAL physical activity monitor and classified as time spent sitting, standing, and stepping. Results In our study population, 562 individuals were obese. 19.4% of the obese individuals and 72.7% of the non-obese individuals was metabolically healthy. After adjustments for age, sex, educational level, smoking, alcohol use, waking time, T2DM, history of CVD and mobility limitation, MHO (n = 107) spent, per day, more time stepping (118.2 versus 105.2 min; p<0.01) and less time sedentary (563.5 versus 593.0 min., p = 0.02) than MUO (n = 440). In parallel, MHNO (n = 1384) spent more time stepping (125.0 versus 115.4 min; p<0.01) and less time sedentary (553.3 versus 576.6 min., p<0.01) than MUNO (n = 518). Conclusion Overall, the metabolically healthy groups were less sedentary and more physically active than the

  19. Metabolic activity and functional diversity changes in sediment prokaryotic communities organically enriched with mussel biodeposits.

    PubMed

    Pollet, Thomas; Cloutier, Olivier; Nozais, Christian; McKindsey, Christopher W; Archambault, Philippe

    2015-01-01

    This experimental microcosm study reports the influence of organic enrichments by mussel biodeposits on the metabolic activity and functional diversity of benthic prokaryotic communities. The different biodeposit enrichment regimes created, which mimicked the quantity of faeces and pseudo-faeces potentially deposited below mussel farms, show a clear stimulatory effect of this organic enrichment on prokaryotic metabolic activity. This effect was detected once a certain level of biodeposition was attained with a tipping point estimated between 3.25 and 10 g day-1 m-2. Prokaryotic communities recovered their initial metabolic activity by 11 days after the cessation of biodeposit additions. However, their functional diversity remained greater than prior to the disturbance suggesting that mussel biodeposit enrichment may disturb the functioning and perhaps the role of prokaryotic communities in benthic ecosystems. This manipulative approach provided new information on the influence of mussel biodeposition on benthic prokaryotic communities and dose-response relationships and may support the development of carrying capacity models for bivalve culture.

  20. Metabolic Activity and Functional Diversity Changes in Sediment Prokaryotic Communities Organically Enriched with Mussel Biodeposits

    PubMed Central

    Pollet, Thomas; Cloutier, Olivier; Nozais, Christian; McKindsey, Christopher W.; Archambault, Philippe

    2015-01-01

    This experimental microcosm study reports the influence of organic enrichments by mussel biodeposits on the metabolic activity and functional diversity of benthic prokaryotic communities. The different biodeposit enrichment regimes created, which mimicked the quantity of faeces and pseudo-faeces potentially deposited below mussel farms, show a clear stimulatory effect of this organic enrichment on prokaryotic metabolic activity. This effect was detected once a certain level of biodeposition was attained with a tipping point estimated between 3.25 and 10 g day-1 m-2. Prokaryotic communities recovered their initial metabolic activity by 11 days after the cessation of biodeposit additions. However, their functional diversity remained greater than prior to the disturbance suggesting that mussel biodeposit enrichment may disturb the functioning and perhaps the role of prokaryotic communities in benthic ecosystems. This manipulative approach provided new information on the influence of mussel biodeposition on benthic prokaryotic communities and dose-response relationships and may support the development of carrying capacity models for bivalve culture. PMID:25923715

  1. Dynamic exometabolome analysis reveals active metabolic pathways in non-replicating mycobacteria.

    PubMed

    Zimmermann, Michael; Kuehne, Andreas; Boshoff, Helena I; Barry, Clifton E; Zamboni, Nicola; Sauer, Uwe

    2015-11-01

    An organism's metabolic activity leaves an extracellular footprint and dynamic changes in this exometabolome inform about nutrient uptake, waste disposal and signalling activities. Using non-targeted mass spectrometry, we report exometabolome dynamics of hypoxia-induced, non-replicating mycobacteria that are thought to play a role in latent tuberculosis. Despite evidence of active metabolism, little is known about the mechanisms enabling obligate aerobic mycobacteria to cope with hypoxia, resulting in long-term survival and increased chemotherapeutic tolerance. The dynamics of 379 extracellular compounds of Mycobacterium smegmatis were deconvoluted with a genome-scale metabolic reaction-pair network to generate hypotheses about intracellular pathway usage. Time-resolved (13) C-tracing and mutant experiments then demonstrated a crucial, energy-generating role of asparagine utilization and non-generic usage of the glyoxylate shunt for hypoxic fitness. Experiments with M. bovis and M. tuberculosis revealed the general relevance of asparagine fermentation and a variable contribution of the glyoxylate shunt to non-replicative, hypoxic survival between the three species.

  2. Unraveling the actions of AMP-activated protein kinase in metabolic diseases: Systemic to molecular insights.

    PubMed

    Weikel, Karen A; Ruderman, Neil B; Cacicedo, José M

    2016-05-01

    AMP-activated protein kinase (AMPK) plays a critical role both in sensing and regulating cellular energy state. In experimental animals, its activation has been shown to reduce the risk of obesity and diabetes-related co-morbidities such as insulin resistance, the metabolic syndrome and atherosclerotic cardiovascular disease. However, in humans, AMPK activation alone often does not completely resolve these conditions. Thus, an improved understanding of AMPK action and regulation in metabolic and other diseases is needed. Herein, we provide a brief description of the enzymatic regulation of AMPK and review its role in maintaining energy homeostasis. We then discuss tissue-specific actions of AMPK that become distorted during such conditions as obesity, type 2 diabetes and certain cancers. Finally, we explore recent findings regarding the interactions of AMPK with mammalian target of rapamycin complex 1 and the lysosome and discuss how changes in these relationships during overnutrition may lead to AMPK dysfunction. A more thorough understanding of AMPK's molecular interactions during diseases of overnutrition may provide key insights for the development of AMPK-based combinatorial treatments for metabolic disease. PMID:27085772

  3. Metabolic activity in dormant conidia of Aspergillus niger and developmental changes during conidial outgrowth.

    PubMed

    Novodvorska, Michaela; Stratford, Malcolm; Blythe, Martin J; Wilson, Raymond; Beniston, Richard G; Archer, David B

    2016-09-01

    The early stages of development of Aspergillus niger conidia during outgrowth were explored by combining genome-wide gene expression analysis (RNAseq), proteomics, Warburg manometry and uptake studies. Resting conidia suspended in water were demonstrated for the first time to be metabolically active as low levels of oxygen uptake and the generation of carbon dioxide were detected, suggesting that low-level respiratory metabolism occurs in conidia for maintenance. Upon triggering of spore germination, generation of CO2 increased dramatically. For a short period, which coincided with mobilisation of the intracellular polyol, trehalose, there was no increase in uptake of O2 indicating that trehalose was metabolised by fermentation. Data from genome-wide mRNA profiling showed the presence of transcripts associated with fermentative and respiratory metabolism in resting conidia. Following triggering of conidial outgrowth, there was a clear switch to respiration after 25min, confirmed by cyanide inhibition. No effect of SHAM, salicylhydroxamic acid, on respiration suggests electron flow via cytochrome c oxidase. Glucose entry into spores was not detectable before 1h after triggering germination. The impact of sorbic acid on germination was examined and we showed that it inhibits glucose uptake. O2 uptake was also inhibited, delaying the onset of respiration and extending the period of fermentation. In conclusion, we show that conidia suspended in water are not completely dormant and that conidial outgrowth involves fermentative metabolism that precedes respiration. PMID:27378203

  4. Modulation of red cell metabolism by states of decreased activation: comparison between states.

    PubMed

    Jevning, R; Wilson, A F; Pirkle, H; Guich, S; Walsh, R N

    1985-11-01

    Marked decline of red cell metabolism has been described during the acute state of decreased activation associated with the stylized mental technique of transcendental meditation (TM) in long-term meditators (5-10 years regular elicitation, TM instructors). It is not known whether unstylized rest is accompanied by a similar effect and it is not known what effector(s) may contribute to red cell metabolic changes in these states. In the present study ordinary, unstylized rest was found to be accompanied by small increase of red cell glycolytic rate. Apparently, either repeated elicitation of TM behavior or some special feature of this practice become associated with new mechanisms of metabolic control than those previously in operation. Although the data of this study do not permit isolation of the precise psychological determinants of this effect, the range of possible physiological effectors can be delimited. Blood pH, PCO2, PO2, and phosphate can be eliminated as significant for red cell metabolic control during both TM and rest, and based upon related studies, several known hormones such as insulin, T3, T4, arginine vasopressin, oxytocin, prolactin and growth hormone can also be eliminated as responsible effector(s).

  5. [Metabolic states at athletes in the strenuous muscular activity of variable character].

    PubMed

    Volkov, N I; Tambovtseva, R V; Iurikov, R V

    2012-01-01

    Investigated dynamics of metabolic conditions at athletes in strenuous muscular activity of variable character. The sportsmen of high qualification specializing in bicycle and skating sports, performed in vitro work on a bicycle ergometer at level of critical power at the maximum consumption of oxygen. In two additional series of experiences each of examinees has performed work on critical power by the initial accelerations making 28% from limiting duration of exercise of 45 and 108 seconds. At work on critical power on a course of performance of exercise consecutive change of metabolic conditions with a phase initial a log-period, fast exponential increase to level of the critical power, the subsequent maintenance of critical power and final dissociation of functions of an aerobic metabolism at increase of local exhaustion was traced. It is established that the most effective concerning work maintenance at level of critical power are short-term (no more than 10 s) initial accelerations on the power corresponding to 45-second limiting exercises: these accelerations stimulate development of functions of an aerobic metabolism and don't lead to exhaustion anaerobic resources and to development of the expressed local exhaustion in the end of work.

  6. Heavy metal effects on the metabolic activity of Elliptio complanata: A calorimetric method

    SciTech Connect

    Cheney, M.A.; Criddle, R.S.

    1996-03-01

    The effects of short time exposure to mercury (Hg{sup 2+}), cadmium (Cd{sup 2+}), and copper (Cu{sup 2+}) ions on the metabolic activity of gill tissue from the freshwater bivalve Elliptio complanata were investigated by isothermal calorimetry and respirometry. Metabolic heat rates were altered following exposure of gill tissue to these ions over the concentration range from 10{sup {minus}6} to 10{sup {minus}3} M. The effects of metal ions on metabolic heat rates were metal ion specific and time and concentration dependent. Treatment of tissue with low concentrations of Hg{sup 2+} and Cu{sup 2+} for short times caused stimulation of metabolic heat rates. Longer exposures and higher concentrations caused inhibition. Cadmium was inhibitory under all conditions tested. Treatment of mitochrondria isolated from gill and muscle tissues showed a similar pattern of stimulation of respiratory rate at low concentration and inhibition at higher concentration. Analysis of CO{sub 2} and O{sub 2} from the headspace gasses in the calorimeter ampule showed an enhancement of respiratory quotient (RQ, i.e., R{sub CO{sub 2}}/R{sub O{sub 2}} where R = rate) following addition of 10{sup {minus}3} M Cd{sup 2+} for 30 min. The microcalorimetric method proved to be a useful technique to assess toxicity of heavy metals on the gills of a freshwater bivalve. 12 refs., 7 figs., 3 tabs.

  7. DIS in AdS

    SciTech Connect

    Albacete, Javier L.; Kovchegov, Yuri V.; Taliotis, Anastasios

    2009-03-23

    We calculate the total cross section for the scattering of a quark-anti-quark dipole on a large nucleus at high energy for a strongly coupled N = 4 super Yang-Mills theory using AdS/CFT correspondence. We model the nucleus by a metric of a shock wave in AdS{sub 5}. We then calculate the expectation value of the Wilson loop (the dipole) by finding the extrema of the Nambu-Goto action for an open string attached to the quark and antiquark lines of the loop in the background of an AdS{sub 5} shock wave. We find two physically meaningful extremal string configurations. For both solutions we obtain the forward scattering amplitude N for the quark dipole-nucleus scattering. We study the onset of unitarity with increasing center-of-mass energy and transverse size of the dipole: we observe that for both solutions the saturation scale Q{sub s} is independent of energy/Bjorken-x and depends on the atomic number of the nucleus as Q{sub s}{approx}A{sup 1/3}. Finally we observe that while one of the solutions we found corresponds to the pomeron intercept of {alpha}{sub P} = 2 found earlier in the literature, when extended to higher energy or larger dipole sizes it violates the black disk limit. The other solution we found respects the black disk limit and yields the pomeron intercept of {alpha}{sub P} = 1.5. We thus conjecture that the right pomeron intercept in gauge theories at strong coupling may be {alpha}{sub P} = 1.5.

  8. Lack of metabolic activation and predominant formation of an excreted metabolite of nontoxic platynecine-type pyrrolizidine alkaloids.

    PubMed

    Ruan, Jianqing; Liao, Cangsong; Ye, Yang; Lin, Ge

    2014-01-21

    Pyrrolizidine alkaloid (PA) poisoning is well-known because of the intake of PA-containing plant-derived natural products and PA-contaminated foodstuffs. Based on different structures of the necine bases, PAs are classified into three types: retronecine, otonecine, and platynecine type. The former two type PAs possessing an unsaturated necine base with a 1,2-double bond are hepatotoxic due to the P450-mediated metabolic activation to generate reactive pyrrolic ester, which interacts with cellular macromolecules leading to toxicity. With a saturated necine base, platynecine-type PAs are reported to be nontoxic and their nontoxicity was hypothesized to be due to the absence of metabolic activation; however, the metabolic pathway responsible for their nontoxic nature is largely unknown. In the present study, to prove the absence of metabolic activation in nontoxic platynecine-type PAs, hepatic metabolism of platyphylline (PLA), a representative platynecine-type PA, was investigated and directly compared with the representatives of two toxic types of PAs in parallel. By determining the pyrrolic ester-derived glutathione conjugate, our results confirmed that the major metabolic pathway of PLA did not lead to formation of the reactive pyrrolic ester. More interestingly, having a metabolic rate similar to that of toxic PAs, PLA also underwent oxidative metabolisms mediated by P450s, especially P450 3A4, the same enzyme that catalyzes metabolic activation of two toxic types of PAs. However, the predominant oxidative dehydrogenation pathway of PLA formed a novel metabolite, dehydroplatyphylline carboxylic acid, which was water-soluble, readily excreted, and could not interact with cellular macromolecules. In conclusion, our study confirmed that the saturated necine bases determine the absence of metabolic activation and thus govern the metabolic pathway responsible for the nontoxic nature of platynecine-type PAs. PMID:24308637

  9. Self-Reported Sitting Time, Physical Activity and Fibrinolytic and Other Novel Cardio-Metabolic Biomarkers in Active Swedish Seniors

    PubMed Central

    Howard, Bethany J.; Hurtig-Wennlöf, Anita; Olsson, Lovisa A.; Nilsson, Torbjörn K.; Dunstan, David W.; Wennberg, Patrik

    2016-01-01

    Background Too much sitting is linked with an increased risk of cardiovascular disease and mortality. The mediating mechanisms for these associations are largely unknown, however dysregulated fibrinolysis have emerged as a possible contributor. Objective We examined the associations of self-reported overall sitting time and physical activity with fibrinolytic and other novel cardio-metabolic biomarkers in older adults. Materials and Methods Data was analysed for 364 participants (74±7 yrs) of the Active Seniors group (retired, living independently in their own homes). Linear regression analyses examined associations of categories of categories of sitting time (≤3, 3–6, >6 hrs/day) and overall physical activity (Low, Moderate and High) with biomarkers in serum or plasma, adjusting for age, gender and smoking (with further adjustment for either overall physical activity or sitting time and BMI in secondary analyses). Results Compared to sitting ≤ 3 hrs/day, sitting >6 hrs/day was associated with higher tissue plasminogen activator (tPA) and tissue plasminogen activator/plasminogen activator inhibitor-1 complex (tPA-PAI-1 complex). These associations were not independent of overall physical activity or BMI. Compared to those in the high physical activity, low physical activity was associated with a higher BMI, high-sensitivity C-reactive protein (hs-CRP) and tPA-PAI-1 complex levels. Only the associations of BMI and hs-CRP were independent of sitting time. Conclusions These findings provide preliminary cross-sectional evidence for the relationships of sitting time with fibrinolytic markers in older adults. They also reinforce the importance of regular physical activity for cardio-metabolic health. PMID:27658041

  10. [Value-Added--Adding Economic Value in the Food Industry].

    ERIC Educational Resources Information Center

    Welch, Mary A., Ed.

    1989-01-01

    This booklet focuses on the economic concept of "value added" to goods and services. A student activity worksheet illustrates how the steps involved in processing food are examples of the concept of value added. The booklet further links food processing to the idea of value added to the Gross National Product (GNP). Discussion questions, a student…

  11. The relationship between microbial metabolic activity and biocorrosion of carbon steel.

    PubMed

    Dzierzewicz, Z; Cwalina, B; Chodurek, E; Wilczok, T

    1997-12-01

    The effect of metabolic activity (expressed by generation time, rate of H2S production and the activity of hydrogenase and adenosine phosphosulphate (APS)-reductase enzymes) of the 8 wild strains of Desulfovibrio desulfuricans and of their resistance to metal ions (Hg2+, Cu2+, Mn2+, Zn2+, Ni2+, Cr3+) on the rate of corrosion of carbon steel was studied. The medium containing lactate as the carbon source and sulphate as the electron acceptor was used for bacterial metabolic activity examination and in corrosive assays. Bacterial growth inhibition by metal ions was investigated in the sulphate-free medium. The rate of H2S production was approximately directly proportional to the specific activities of the investigated enzymes. These activities were inversely proportional to the generation time. The rate of microbiologically induced corrosion (MIC) of carbon steel was directly proportional to bacterial resistance to metal ions (correlation coefficient r = 0.95). The correlation between the MIC rate and the activity of enzymes tested, although weaker, was also observed (r = 0.41 for APS-reductase; r = 0.69 for hydrogenase; critical value rc = 0.30, p = 0.05, n = 40).

  12. Evolution of a new chlorophyll metabolic pathway driven by the dynamic changes in enzyme promiscuous activity.

    PubMed

    Ito, Hisashi; Tanaka, Ayumi

    2014-03-01

    Organisms generate an enormous number of metabolites; however, the mechanisms by which a new metabolic pathway is acquired are unknown. To elucidate the importance of promiscuous enzyme activity for pathway evolution, the catalytic and substrate specificities of Chl biosynthetic enzymes were examined. In green plants, Chl a and Chl b are interconverted by the Chl cycle: Chl a is hydroxylated to 7-hydroxymethyl chlorophyll a followed by the conversion to Chl b, and both reactions are catalyzed by chlorophyllide a oxygenase. Chl b is reduced to 7-hydroxymethyl chlorophyll a by Chl b reductase and then converted to Chl a by 7-hydroxymethyl chlorophyll a reductase (HCAR). A phylogenetic analysis indicated that HCAR evolved from cyanobacterial 3,8-divinyl chlorophyllide reductase (DVR), which is responsible for the reduction of an 8-vinyl group in the Chl biosynthetic pathway. In addition to vinyl reductase activity, cyanobacterial DVR also has Chl b reductase and HCAR activities; consequently, three of the four reactions of the Chl cycle already existed in cyanobacteria, the progenitor of the chloroplast. During the evolution of cyanobacterial DVR to HCAR, the HCAR activity, a promiscuous reaction of cyanobacterial DVR, became the primary reaction. Moreover, the primary reaction (vinyl reductase activity) and some disadvantageous reactions were lost, but the neutral promiscuous reaction (NADH dehydrogenase) was retained in both DVR and HCAR. We also show that a portion of the Chl c biosynthetic pathway already existed in cyanobacteria. We discuss the importance of dynamic changes in promiscuous activity and of the latent pathways for metabolic evolution.

  13. Effect of contrasted levels of habitual physical activity on metabolic flexibility.

    PubMed

    Bergouignan, Audrey; Antoun, Edwina; Momken, Iman; Schoeller, Dale A; Gauquelin-Koch, Guillemette; Simon, Chantal; Blanc, Stéphane

    2013-02-01

    The factors regulating the body's ability to switch from fat to carbohydrate oxidation in response to fuel availability changes, or metabolic flexibility (MF), are currently intensively investigated in the context of metabolic diseases. Although numerous metabolic diseases are associated with sedentary behaviors and metabolic inflexibility, the effect of habitual physical activity level (PAL) on MF regulation is surprisingly poorly known. We investigated how PAL affects MF in cross-sectional and interventional studies. MF was assessed in 44 subjects: normal-weight and overweight sedentary men submitted to 2 mo of exercise at current recommendations, normal-weight active men submitted to 1 mo of reduced PAL and normal-weight women submitted to 1 mo of bed rest, with or without exercise. MF was evaluated, before and after interventions, following two standard meals as the relationship between individual mathematical variances in insulin and nonprotein respiratory quotient (NPRQ) daily kinetics. Daily NPRQ and insulin variances differed according to habitual PAL (P = 0.002 and P = 0.009, respectively); active subjects had higher variances in NPRQ for lower variances in insulin than sedentary subjects, indicating a better MF. Detraining increased insulin variance (P = 0.009) and decreased NPRQ variance (P = 0.003), while training tended to have opposite effects. Insulin and NPRQ variances were negatively related along the PAL continuum (R(2) = 0.70, P < 0.001). Variance in NPRQ was also positively related to PAL (R(2) = 0.52, P < 0.001). By assessing MF with mathematical surrogates in conditions of daily pattern in meal's intake, we showed that habitual PAL is associated with MF status, and that MF is modulated by changes in PAL. PMID:23239872

  14. Effect of contrasted levels of habitual physical activity on metabolic flexibility.

    PubMed

    Bergouignan, Audrey; Antoun, Edwina; Momken, Iman; Schoeller, Dale A; Gauquelin-Koch, Guillemette; Simon, Chantal; Blanc, Stéphane

    2013-02-01

    The factors regulating the body's ability to switch from fat to carbohydrate oxidation in response to fuel availability changes, or metabolic flexibility (MF), are currently intensively investigated in the context of metabolic diseases. Although numerous metabolic diseases are associated with sedentary behaviors and metabolic inflexibility, the effect of habitual physical activity level (PAL) on MF regulation is surprisingly poorly known. We investigated how PAL affects MF in cross-sectional and interventional studies. MF was assessed in 44 subjects: normal-weight and overweight sedentary men submitted to 2 mo of exercise at current recommendations, normal-weight active men submitted to 1 mo of reduced PAL and normal-weight women submitted to 1 mo of bed rest, with or without exercise. MF was evaluated, before and after interventions, following two standard meals as the relationship between individual mathematical variances in insulin and nonprotein respiratory quotient (NPRQ) daily kinetics. Daily NPRQ and insulin variances differed according to habitual PAL (P = 0.002 and P = 0.009, respectively); active subjects had higher variances in NPRQ for lower variances in insulin than sedentary subjects, indicating a better MF. Detraining increased insulin variance (P = 0.009) and decreased NPRQ variance (P = 0.003), while training tended to have opposite effects. Insulin and NPRQ variances were negatively related along the PAL continuum (R(2) = 0.70, P < 0.001). Variance in NPRQ was also positively related to PAL (R(2) = 0.52, P < 0.001). By assessing MF with mathematical surrogates in conditions of daily pattern in meal's intake, we showed that habitual PAL is associated with MF status, and that MF is modulated by changes in PAL.

  15. Detection of metabolic activation leading to drug-induced phospholipidosis in rat hepatocyte spheroids.

    PubMed

    Takagi, Masashi; Sanoh, Seigo; Santoh, Masataka; Ejiri, Yoko; Kotake, Yaichiro; Ohta, Shigeru

    2016-02-01

    Drug-induced phospholipidosis (PLD) is one of the adverse reactions to treatment with cationic amphiphilic drugs. Recently, simple and reliable evaluation methods for PLD have been reported. However, the predictive power of these methods for in vivo PLD induction is insufficient in some cases. To accurately predict PLD, we focused on drug metabolism and used three-dimensional cultures of hepatocytes known as spheroids. Here we used the fluorescent phospholipid dye N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine (NBD-PE) to detect PLD induction. After 48 hr exposure to 20 µM amiodarone and amitriptyline, PLD inducers, NBD-PE fluorescence in the spheroids was significantly higher than that in the control. In contrast, 1 mM acetaminophen, as a negative control, did not increase fluorescence. Furthermore, the combination of NBD-PE fluorescence and LysoTracker Red fluorescence and the accumulation of intrinsic phospholipids reflected PLD induction in spheroids. To evaluate metabolic activation, we assessed PLD induction by loratadine. NBD-PE fluorescence intensity was significantly increased by 50 µM loratadine treatment. However, the fluorescence was markedly decreased by co-treatment with 500 µM 1-aminobenzotriazole, a broad cytochrome P450 inhibitor. The formation of desloratadine, a metabolite of loratadine, was observed in spheroids after treatment with loratadine alone. These results showed that metabolic activation is the key factor in PLD induction by treatment with loratadine. We demonstrated that rat primary hepatocyte spheroid culture is a useful model for evaluating drug-induced PLD induction mediated by metabolic activation of the drug using the fluorescence probe technique. PMID:26763403

  16. Compartment-specific activation of PPARγ governs breast cancer tumor growth, via metabolic reprogramming and symbiosis.

    PubMed

    Avena, Paola; Anselmo, Wanda; Whitaker-Menezes, Diana; Wang, Chenguang; Pestell, Richard G; Lamb, Rebecca S; Hulit, James; Casaburi, Ivan; Andò, Sebastiano; Martinez-Outschoorn, Ubaldo E; Lisanti, Michael P; Sotgia, Federica

    2013-05-01

    The role of PPARγ in cancer therapy is controversial, with studies showing either pro-tumorigenic or antineoplastic effects. This debate is very clinically relevant, because PPARγ agonists are used as antidiabetic drugs. Here, we evaluated if the effects of PPARγ on tumorigenesis are determined by the cell type in which PPARγ is activated. Second, we examined if the metabolic changes induced by PPARγ, such as glycolysis and autophagy, play any role in the tumorigenic process. To this end, PPARγ was overexpressed in breast cancer cells or in stromal cells. PPARγ-overexpressing cells were examined with respect to (1) their tumorigenic potential, using xenograft models, and (2) regarding their metabolic features. In xenograft models, we show that when PPARγ is activated in cancer cells, tumor growth is inhibited by 40%. However, when PPARγ is activated in stromal cells, the growth of co-injected breast cancer cells is enhanced by 60%. Thus, the effect(s) of PPARγ on tumorigenesis are dependent on the cell compartment in which PPARγ is activated. Mechanistically, stromal cells with activated PPARγ display metabolic features of cancer-associated fibroblasts, with increased autophagy, glycolysis and senescence. Indeed, fibroblasts overexpressing PPARγ show increased expression of autophagic markers, increased numbers of acidic autophagic vacuoles, increased production of L-lactate, cell hypertrophy and mitochondrial dysfunction. In addition, PPARγ fibroblasts show increased expression of CDKs (p16/p21) and β-galactosidase, which are markers of cell cycle arrest and senescence. Finally, PPARγ induces the activation of the two major transcription factors that promote autophagy and glycolysis, i.e., HIF-1α and NFκB, in stromal cells. Thus, PPARγ activation in stromal cells results in the formation of a catabolic pro-inflammatory microenvironment that metabolically supports cancer growth. Interestingly, the tumor inhibition observed when PPARγ is

  17. Estrogen receptor alpha activation enhances mitochondrial function and systemic metabolism in high-fat-fed ovariectomized mice.

    PubMed

    Hamilton, Dale J; Minze, Laurie J; Kumar, Tanvi; Cao, Tram N; Lyon, Christopher J; Geiger, Paige C; Hsueh, Willa A; Gupte, Anisha A

    2016-09-01

    Estrogen impacts insulin action and cardiac metabolism, and menopause dramatically increases cardiometabolic risk in women. However, the mechanism(s) of cardiometabolic protection by estrogen remain incompletely understood. Here, we tested the effects of selective activation of E2 receptor alpha (ERα) on systemic metabolism, insulin action, and cardiac mitochondrial function in a mouse model of metabolic dysfunction (ovariectomy [OVX], insulin resistance, hyperlipidemia, and advanced age). Middle-aged (12-month-old) female low-density lipoprotein receptor (Ldlr)(-/-) mice were subjected to OVX or sham surgery and fed "western" high-fat diet (WHFD) for 3 months. Selective ERα activation with 4,4',4″-(4-Propyl-[1H]-pyrazole-1,3,5-triyl) (PPT), prevented weight gain, improved insulin action, and reduced visceral fat accumulation in WHFD-fed OVX mice. PPT treatment also elevated systemic metabolism, increasing oxygen consumption and core body temperature, induced expression of several metabolic genes such as peroxisome proliferator-activated receptor gamma, coactivator 1 alpha, and nuclear respiratory factor 1 in heart, liver, skeletal muscle, and adipose tissue, and increased cardiac mitochondrial function. Taken together, selective activation of ERα with PPT enhances metabolic effects including insulin resistance, whole body energy metabolism, and mitochondrial function in OVX mice with metabolic syndrome. PMID:27582063

  18. Influence of uranium (VI) on the metabolic activity of stable multispecies biofilms studied by oxygen microsensors and fluorescence microscopy

    NASA Astrophysics Data System (ADS)

    Krawczyk-Bärsch, Evelyn; Grossmann, Kay; Arnold, Thuro; Hofmann, Susann; Wobus, Axel

    2008-11-01

    The effect of uranium added in ecologically relevant concentrations (1 × 10 -5 and 1 × 10 -6 M) to stable multispecies biofilms was studied by electrochemical oxygen microsensors with tip diameters of 10 μm and by confocal laser fluorescence microscopy (CLSM). The microsensor profile measurements in the stable multispecies biofilms exposed to uranium showed that the oxygen concentration decreased faster with increasing biofilm depth compared to the uranium free biofilms. In the uranium containing biofilms, the oxygen consumption, calculated from the steady-state microprofiles, showed high consumption rates of up to 61.7 nmol cm -3 s -1 in the top layer (0-70 μm) and much lower consumption rates in the lower zone of the biofilms. Staining experiments with 5-cyano-2,3-ditolyl tetrazolium chloride (CTC) and 4,6-diamidino-2-phenylindole (DAPI) confirmed the high respiratory activities of the bacteria in the upper layer. Analysis of the amplified 16S rRNA gene fragments showed that the addition of uranium in ecologically relevant concentrations did not change the bacterial diversity in the stable multispecies biofilms and is therefore not responsible for the different oxygen profiles in the biofilms. The fast decrease in the oxygen concentrations in the biofilm profiles showed that the bacteria in the top region of the biofilms, i.e., the metabolically most active biofilm zone, battle the toxic effects of aqueous uranium with an increased respiratory activity. This increased respiratory activity results in O 2 depleted zones closer to the biofilm/air interface which may trigger uranium redox processes, since suitable redox partners, e.g., extracellular polymeric substance (EPS) and other organics (e.g., metabolites), are sufficiently available in the biofilm porewaters. Such redox reactions may lead to precipitation of uranium (IV) solids and consequently to a removal of uranium from the aqueous phase.

  19. Transcriptional activity of the giant barrel sponge, Xestospongia muta Holobiont: molecular evidence for metabolic interchange

    PubMed Central

    Fiore, Cara L.; Labrie, Micheline; Jarett, Jessica K.; Lesser, Michael P.

    2015-01-01

    Compared to our understanding of the taxonomic composition of the symbiotic microbes in marine sponges, the functional diversity of these symbionts is largely unknown. Furthermore, the application of genomic, transcriptomic, and proteomic techniques to functional questions on sponge host-symbiont interactions is in its infancy. In this study, we generated a transcriptome for the host and a metatranscriptome of its microbial symbionts for the giant barrel sponge, Xestospongia muta, from the Caribbean. In combination with a gene-specific approach, our goals were to (1) characterize genetic evidence for nitrogen cycling in X. muta, an important limiting nutrient on coral reefs (2) identify which prokaryotic symbiont lineages are metabolically active and, (3) characterize the metabolic potential of the prokaryotic community. Xestospongia muta expresses genes from multiple nitrogen transformation pathways that when combined with the abundance of this sponge, and previous data on dissolved inorganic nitrogen fluxes, shows that this sponge is an important contributor to nitrogen cycling biogeochemistry on coral reefs. Additionally, we observed significant differences in gene expression of the archaeal amoA gene, which is involved in ammonia oxidation, between coral reef locations consistent with differences in the fluxes of dissolved inorganic nitrogen previously reported. In regards to symbiont metabolic potential, the genes in the biosynthetic pathways of several amino acids were present in the prokaryotic metatranscriptome dataset but in the host-derived transcripts only the catabolic reactions for these amino acids were present. A similar pattern was observed for the B vitamins (riboflavin, biotin, thiamin, cobalamin). These results expand our understanding of biogeochemical cycling in sponges, and the metabolic interchange highlighted here advances the field of symbiont physiology by elucidating specific metabolic pathways where there is high potential for host

  20. Early and current physical activity: relationship with intima-media thickness and metabolic variables in adulthood

    PubMed Central

    Lima, Manoel C. S.; Barbosa, Maurício F.; Diniz, Tiego A.; Codogno, Jamile S.; Freitas, Ismael F.; Fernandes, Rômulo A.

    2014-01-01

    Background: It is unclear whether early physical activity has a greater influence on intima-media thickness and metabolic variables than current physical activity. Objective: To analyze the relationship between current and early physical activity, metabolic variables, and intima-media thickness measures in adults. Method: The sample was composed of 55 healthy subjects of both sexes (33 men and 22 women). Total body fat and trunk fat were estimated by dual-energy X-ray absorptiometry. Carotid and femoral intima-media thickness were measured using a Doppler ultrasound device. A 12-hour fasting blood sample collection was taken (fasting glucose and lipid profile). Early physical activity was assessed through face-to-face interview, and the current physical activity was assessed by pedometer (Digi-Walker Yamax, SW200), which was used for a period of seven days. Results: Current physical activity was negatively related to total cholesterol (rho=-0.31), while early physical activity was negatively related to triglycerides (rho=-0.42), total cholesterol (rho=-0.28), very low density lipoprotein (rho=-0.44), and carotid intima-media thickness (rho=-0.50). In the multivariate model, subjects engaged in sports activities during early life had lower values of very low density lipoprotein (b=-8.74 [b=-16.1; -1.47]) and carotid intima-media thickness (b=-0.17 [95%CI: -0.28; -0.05]). Conclusion: Early 95%CI physical activity has a significant influence on carotid intima-media thickness, regardless of the current physical activity. PMID:25372009

  1. Transcriptional profiling unravels potential metabolic activities of the olive leaf non-glandular trichome

    PubMed Central

    Koudounas, Konstantinos; Manioudaki, Maria E.; Kourti, Anna; Banilas, Georgios; Hatzopoulos, Polydefkis

    2015-01-01

    The olive leaf trichomes are multicellular peltate hairs densely distributed mainly at the lower leaf epidermis. Although, non-glandular, they have gained much attention since they significantly contribute to abiotic and biotic stress tolerance of olive leaves. The exact mechanisms by which olive trichomes achieve these goals are not fully understood. They could act as mechanical barrier but they also accumulate high amounts of flavonoids among other secondary metabolites. However, little is currently known about the exact compounds they produce and the respective metabolic pathways. Here we present the first EST analysis from olive leaf trichomes by using 454-pyrosequencing. A total of 5368 unigenes were identified out of 7258 high quality reads with an average length of 262 bp. Blast search revealed that 27.5% of them had high homologies to known proteins. By using Blast2GO, 1079 unigenes (20.1%) were assigned at least one Gene Ontology (GO) term. Most of the genes were involved in cellular and metabolic processes and in binding functions followed by catalytic activity. A total of 521 transcripts were mapped to 67 KEGG pathways. Olive trichomes represent a tissue of highly unique transcriptome as per the genes involved in developmental processes and the secondary metabolism. The results indicate that mature olive trichomes are trancriptionally active, mainly through the potential production of enzymes that contribute to phenolic compounds with important roles in biotic and abiotic stress responses. PMID:26322070

  2. Nur77 modulates hepatic lipid metabolism through suppression of SREBP1c activity

    SciTech Connect

    Pols, Thijs W.H.; Ottenhoff, Roelof; Vos, Mariska; Levels, Johannes H.M.; Quax, Paul H.A.; Meijers, Joost C.M.; Pannekoek, Hans; Groen, Albert K.; Vries, Carlie J.M. de

    2008-02-22

    NR4A nuclear receptors are induced in the liver upon fasting and regulate hepatic gluconeogenesis. Here, we studied the role of nuclear receptor Nur77 (NR4A1) in hepatic lipid metabolism. We generated mice expressing hepatic Nur77 using adenoviral vectors, and demonstrate that these mice exhibit a modulation of the plasma lipid profile and a reduction in hepatic triglyceride. Expression analysis of >25 key genes involved in lipid metabolism revealed that Nur77 inhibits SREBP1c expression. This results in decreased SREBP1c activity as is illustrated by reduced expression of its target genes stearoyl-coA desaturase-1, mitochondrial glycerol-3-phosphate acyltransferase, fatty acid synthase and the LDL receptor, and provides a mechanism for the physiological changes observed in response to Nur77. Expression of LXR target genes Abcg5 and Abcg8 is reduced by Nur77, and may suggest involvement of LXR in the inhibitory action of Nur77 on SREBP1c expression. Taken together, our study demonstrates that Nur77 modulates hepatic lipid metabolism through suppression of SREBP1c activity.

  3. Blood flow to long bones indicates activity metabolism in mammals, reptiles and dinosaurs.

    PubMed

    Seymour, Roger S; Smith, Sarah L; White, Craig R; Henderson, Donald M; Schwarz-Wings, Daniela

    2012-02-01

    The cross-sectional area of a nutrient foramen of a long bone is related to blood flow requirements of the internal bone cells that are essential for dynamic bone remodelling. Foramen area increases with body size in parallel among living mammals and non-varanid reptiles, but is significantly larger in mammals. An index of blood flow rate through the foramina is about 10 times higher in mammals than in reptiles, and even higher if differences in blood pressure are considered. The scaling of foramen size correlates well with maximum whole-body metabolic rate during exercise in mammals and reptiles, but less well with resting metabolic rate. This relates to the role of blood flow associated with bone remodelling during and following activity. Mammals and varanid lizards have much higher aerobic metabolic rates and exercise-induced bone remodelling than non-varanid reptiles. Foramen areas of 10 species of dinosaur from five taxonomic groups are generally larger than from mammals, indicating a routinely highly active and aerobic lifestyle. The simple measurement holds possibilities offers the possibility of assessing other groups of extinct and living vertebrates in relation to body size, behaviour and habitat.

  4. Colchicine to decrease NLRP3-activated inflammation and improve obesity-related metabolic dysregulation.

    PubMed

    Demidowich, Andrew P; Davis, Angela I; Dedhia, Nicket; Yanovski, Jack A

    2016-07-01

    Obesity is a major risk-factor for the development of insulin resistance, type 2 diabetes, and cardiovascular disease. Circulating molecules associated with obesity, such as saturated fatty acids and cholesterol crystals, stimulate the innate immune system to incite a chronic inflammatory state. Studies in mouse models suggest that suppressing the obesity-induced chronic inflammatory state may prevent or reverse obesity-associated metabolic dysregulation. Human studies, however, have been far less positive, possibly because targeted interventions were too far downstream of the inciting inflammatory events. Recently, it has been shown that, within adipose tissue macrophages, assembly of a multi-protein member of the innate immune system, the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, is essential for the induction of this inflammatory state. Microtubules enable the necessary spatial arrangement of the components of the NLRP3 inflammasome in the cell, leading to its activation and propagation of the inflammatory cascade. Colchicine, a medication classically used for gout, mediates its anti-inflammatory effect by inhibiting tubulin polymerization, and has been shown to attenuate macrophage NLRP3 inflammasome arrangement and activation in vitro and in vivo. Given these findings, we hypothesize that, in at-risk individuals (those with obesity-induced inflammation and metabolic dysregulation), long-term colchicine use will lead to suppression of inflammation and thus cause improvements in insulin sensitivity and other obesity-related metabolic impairments. PMID:27241260

  5. Metabolism of Preimplantation Embryo Development: A Bystander or an Active Participant?

    PubMed

    Kaneko, K J

    2016-01-01

    Unicellular organisms are exquisitely sensitive to nutrient availability in the environment and have evolved elaborate mechanisms to sense the levels and types of nutrients, altering gene expression patterns accordingly to adjust the metabolic activities required to survive. Thus, environmental cues induce adaptive metabolic differentiation through transcriptional and posttranscriptional changes. Similarly, preimplantation embryos are exposed to various environmental cues within the maternal reproductive tract prior to implantation. Because only "simple" culture conditions are required, it is assumed that these embryos are genetically preprogrammed to develop with little influence from the environment, with the exception of few "necessities" provided by the environment. However, a wealth of literature now suggests that the developing embryos are greatly influenced by the maternal environment. Even though the developing embryos have the capacity and plasticity to deal with nutritional imbalance posed by an altered maternal environment, there is often a trade-off to the overall fitness of those embryos later in life. Despite these studies that underline the general importance of the reproductive environment during development, it is thought that the primary driver of mammalian development is strictly genetic and that metabolic adaptation by the preimplantation embryo is secondary to genetic control. In this review, I propose that not only does the maternal environment of developing preimplantation embryos influence developmental potential, pregnancy outcomes, and postnatal disease states, but that it has an active role in induction and potentiation of the first differentiation event, the production of trophectoderm and inner cell mass lineages. PMID:27475855

  6. Inner workings of thrombolites: spatial gradients of metabolic activity as revealed by metatranscriptome profiling

    PubMed Central

    Mobberley, J. M.; Khodadad, C. L. M.; Visscher, P. T.; Reid, R. P.; Hagan, P.; Foster, J. S.

    2015-01-01

    Microbialites are sedimentary deposits formed by the metabolic interactions of microbes and their environment. These lithifying microbial communities represent one of the oldest ecosystems on Earth, yet the molecular mechanisms underlying the function of these communities are poorly understood. In this study, we used comparative metagenomic and metatranscriptomic analyses to characterize the spatial organization of the thrombolites of Highborne Cay, The Bahamas, an actively forming microbialite system. At midday, there were differences in gene expression throughout the spatial profile of the thrombolitic mat with a high abundance of transcripts encoding genes required for photosynthesis, nitrogen fixation and exopolymeric substance production in the upper three mm of the mat. Transcripts associated with denitrification and sulfate reduction were in low abundance throughout the depth profile, suggesting these metabolisms were less active during midday. Comparative metagenomics of the Bahamian thrombolites with other known microbialite ecosystems from across the globe revealed that, despite many shared core pathways, the thrombolites represented genetically distinct communities. This study represents the first time the metatranscriptome of living microbialite has been characterized and offers a new molecular perspective on those microbial metabolisms, and their underlying genetic pathways, that influence the mechanisms of carbonate precipitation in lithifying microbial mat ecosystems. PMID:26213359

  7. Inner workings of thrombolites: spatial gradients of metabolic activity as revealed by metatranscriptome profiling

    NASA Astrophysics Data System (ADS)

    Mobberley, J. M.; Khodadad, C. L. M.; Visscher, P. T.; Reid, R. P.; Hagan, P.; Foster, J. S.

    2015-07-01

    Microbialites are sedimentary deposits formed by the metabolic interactions of microbes and their environment. These lithifying microbial communities represent one of the oldest ecosystems on Earth, yet the molecular mechanisms underlying the function of these communities are poorly understood. In this study, we used comparative metagenomic and metatranscriptomic analyses to characterize the spatial organization of the thrombolites of Highborne Cay, The Bahamas, an actively forming microbialite system. At midday, there were differences in gene expression throughout the spatial profile of the thrombolitic mat with a high abundance of transcripts encoding genes required for photosynthesis, nitrogen fixation and exopolymeric substance production in the upper three mm of the mat. Transcripts associated with denitrification and sulfate reduction were in low abundance throughout the depth profile, suggesting these metabolisms were less active during midday. Comparative metagenomics of the Bahamian thrombolites with other known microbialite ecosystems from across the globe revealed that, despite many shared core pathways, the thrombolites represented genetically distinct communities. This study represents the first time the metatranscriptome of living microbialite has been characterized and offers a new molecular perspective on those microbial metabolisms, and their underlying genetic pathways, that influence the mechanisms of carbonate precipitation in lithifying microbial mat ecosystems.

  8. Metabolic activation by hamster and rat hepatocytes in the Salmonella mutagenicity assay.

    PubMed

    Poiley, J A; Raineri, R; Andrews, A W; Cavanaugh, D M; Pienta, R J

    1980-12-01

    Intact and homogenized hepatocytes from untreated or Aroclor 1254-treated male and female noninbred Sprague-Dawley rats and noninbred Syrian golden hamsters were compared for their ability to metabolize chemicals in the Salmonella-mammalian microsome mutagenesis assay. The following chemicals were used: two aromatic amines, 2-amino-anthracene and N-2-fluorenylacetamide; two polycyclic aromatic hydrocarbons, 3-methylcholanthrene and benzo[a]pyrene (BP); and one nitrosamine, diethylnitrosamine (DENA). With one exception, hepatocytes from hamsters were more active than were hepatocytes from rats in the activation of these mutagens. The homogenized preparations from Aroclor 1254-treated rats were slightly more active with BP than was the equivalent hamster preparation. Intact hepatocytes from Aroclor 1254-treated hamsters were more efficient at metabolizing the aromatic amines and DENA, whereas homogenates were more effective with the hydrocarbons. Results were similar with the rat preparations, except that only large quantities of Aroclor 1254-treated intact male rat hepatocytes appeared to activate DENA. These results suggest that, in the choice of an activation system, the kind of chemical being evaluated should be considered.

  9. Testosterone affects hormone-sensitive lipase (HSL) activity and lipid metabolism in the left ventricle.

    PubMed

    Langfort, Jozef; Jagsz, Slawomir; Dobrzyn, Pawel; Brzezinska, Zofia; Klapcinska, Barbara; Galbo, Henrik; Gorski, Jan

    2010-09-01

    Fatty acids, which are the major cardiac fuel, are derived from lipid droplets stored in cardiomyocytes, among other sources. The heart expresses hormone-sensitive lipase (HSL), which regulates triglycerides (TG) breakdown, and the enzyme is under hormonal control. Evidence obtained from adipose tissue suggests that testosterone regulates HSL activity. To test whether this is also true in the heart, we measured HSL activity in the left ventricle of sedentary male rats that had been treated with testosterone supplementation or orchidectomy with or without testosterone substitution. Left ventricle HSL activity against TG was significantly elevated in intact rats supplemented with testosterone. HSL activity against both TG and diacylglyceride was reduced by orchidectomy, whereas testosterone replacement fully reversed this effect. Moreover, testosterone increased left ventricle free fatty acid levels, caused an inhibitory effect on carbohydrate metabolism in the heart, and elevated left ventricular phosphocreatine and ATP levels as compared to control rats. These data indicate that testosterone is involved in cardiac HSL activity regulation which, in turn, may affect cardiac lipid and carbohydrate metabolism.

  10. Adenosine monophosphate-activated protein kinase activation, substrate transporter translocation, and metabolism in the contracting hyperthyroid rat heart.

    PubMed

    Heather, Lisa C; Cole, Mark A; Atherton, Helen J; Coumans, Will A; Evans, Rhys D; Tyler, Damian J; Glatz, Jan F C; Luiken, Joost J F P; Clarke, Kieran

    2010-01-01

    Thyroid hormones can modify cardiac metabolism via multiple molecular mechanisms, yet their integrated effect on overall substrate metabolism is poorly understood. Here we determined the effect of hyperthyroidism on substrate metabolism in the isolated, perfused, contracting rat heart. Male Wistar rats were injected for 7 d with T(3) (0.2 mg/kg x d ip). Plasma free fatty acids increased by 97%, heart weights increased by 33%, and cardiac rate pressure product, an indicator of contractile function, increased by 33% in hyperthyroid rats. Insulin-stimulated glycolytic rates and lactate efflux rates were increased by 33% in hyperthyroid rat hearts, mediated by an increased insulin-stimulated translocation of the glucose transporter GLUT4 to the sarcolemma. This was accompanied by a 70% increase in phosphorylated AMP-activated protein kinase (AMPK) and a 100% increase in phosphorylated acetyl CoA carboxylase, confirming downstream signaling from AMPK. Fatty acid oxidation rates increased in direct proportion to the increased heart weight and rate pressure product in the hyperthyroid heart, mediated by synchronized changes in mitochondrial enzymes and respiration. Protein levels of the fatty acid transporter, fatty acid translocase (FAT/CD36), were reduced by 24% but were accompanied by a 19% increase in the sarcolemmal content of fatty acid transport protein 1 (FATP1). Thus, the relationship between fatty acid metabolism, cardiac mass, and contractile function was maintained in the hyperthyroid heart, associated with a sarcolemmal reorganization of fatty acid transporters. The combined effects of T(3)-induced AMPK activation and insulin stimulation were associated with increased sarcolemmal GLUT4 localization and glycolytic flux in the hyperthyroid heart. PMID:19940039

  11. 2D-Visualization of metabolic activity with planar optical chemical sensors (optodes)

    NASA Astrophysics Data System (ADS)

    Meier, R. J.; Liebsch, G.

    2015-12-01

    Microbia plays an outstandingly important role in many hydrologic compartments, such as e.g. the benthic community in sediments, or biologically active microorganisms in the capillary fringe, in ground water, or soil. Oxygen, pH, and CO2 are key factors and indicators for microbial activity. They can be measured using optical chemical sensors. These sensors record changing fluorescence properties of specific indicator dyes. The signals can be measured in a non-contact mode, even through transparent walls, which is important for many lab-experiments. They can measure in closed (transparent) systems, without sampling or intruding into the sample. They do not consume the analytes while measuring, are fully reversible and able to measure in non-stirred solutions. These sensors can be applied as high precision fiberoptic sensors (for profiling), robust sensor spots, or as planar sensors for 2D visualization (imaging). Imaging enables to detect thousands of measurement spots at the same time and generate 2D analyte maps over a region of interest. It allows for comparing different regions within one recorded image, visualizing spatial analyte gradients, or more important to identify hot spots of metabolic activity. We present ready-to-use portable imaging systems for the analytes oxygen, pH, and CO2. They consist of a detector unit, planar sensor foils and a software for easy data recording and evaluation. Sensors foils for various analytes and measurement ranges enable visualizing metabolic activity or analyte changes in the desired range. Dynamics of metabolic activity can be detected in one shot or over long time periods. We demonstrate the potential of this analytical technique by presenting experiments on benthic disturbance-recovery dynamics in sediments and microbial degradation of organic material in the capillary fringe. We think this technique is a new tool to further understand how microbial and geochemical processes are linked in (not solely) hydrologic

  12. The "aged garlic extract:" (AGE) and one of its active ingredients S-allyl-L-cysteine (SAC) as potential preventive and therapeutic agents for Alzheimer's disease (AD).

    PubMed

    Ray, B; Chauhan, N B; Lahiri, D K

    2011-01-01

    Alzheimer's disease (AD) is the most common form of dementia in the older people and 7(th) leading cause of death in the United States. Deposition of amyloid-beta (Aβ) plaques, hyperphosphorylation of microtubule associated protein tau (MAPT), neuroinflammation and cholinergic neuron loss are the major hallmarks of AD. Deposition of Aβ peptides, which takes place years before the clinical onset of the disease can trigger hyperphophorylation of tau proteins and neuroinflammation, and the latter is thought to be primarily involved in neuronal and synaptic damage seen in AD. To date, four cholinesterase inhibitors or ChEI (tacrine, rivastigmine, donepezil and galantamine) and a partial NMDA receptor antagonist (memantine) are the only approved treatment options for AD. However, these drugs fail to completely cure the disease, which warrants a search for newer class of targets that would eventually lead to effective drugs for the treatment of AD. In addition to selected pharmacological agents, botanical and medicinal plant extracts are also being investigated. Apart from its culinary use, garlic (Allium sativum) is being used to treat several ailments like cancer and diabetes. Herein we have discussed the effects of a specific 'Aged Garlic Extract' (AGE) and one of its active ingredients, S-allyl-L-cysteine (SAC) in restricting several pathological cascades related to the synaptic degeneration and neuroinflammatory pathways associated with AD. Thus, based on the reported positive preliminary results reviewed herein, further research is required to develop the full potential of AGE and/or SAC into an effective preventative strategy for AD. PMID:21728972

  13. Activation of phosphatidic acid metabolism of human erythrocyte membranes by perfringolysin O

    SciTech Connect

    Saito, M.; Ando, S.; Mitsui, K.; Homma, Y.; Takenawa, T.

    1986-05-29

    The effect of perfringolysin O on the lipid metabolism of human erythrocyte membranes was investigated. Erythrocytes were prelabeled with (/sup 3/H)arachidonic acid and (/sup 32/P)inorganic phosphate. In the presence of calcium ion (5.5 mM), the effect of perfringolysin O on lipid metabolism was very similar to that of an calcium-ionophore A23187. In the absence of calcium ion, the accumulation of phosphatidic acid and its following decreasing trend were observed during the reaction with the toxin. Such changes were not caused by filipin. These results suggest that perfringolysin O causes the activation of a diglyceride-phosphatidic acid cycle, which might be involved in the calcium transport.

  14. Correlation between phagocytic activity and metabolic response of polymorphonuclear leukocytes toward different strains of Escherichia coli.

    PubMed Central

    Rottini, G; Dri, P; Soranzo, M R; Patriarca, P

    1975-01-01

    The bactericidal activity, the phagocytic capacity, and the metabolic stimulation of polymorphonuclear leukocytes challenged with different strains of Escherichia coli were studied. It was found that only two strains out of 10 tested stimulated the oxygen consumption and carbohydrate metabolism of leukocytes and were readily killed by the phagocytes. The lack of killing of the other eight strains was shown to be due to absent or poor phagocytosis rather than to resistance to intracellular killing. Evidence was presented that the surface K antigen plays an important role in conferring antiphagocytic properties to some strains of E. coli. It was suggested that K antigen acts by interfering with the early step of the phagocytic process, that is, the attachment step. PMID:1090529

  15. Cytochromes P450 and species differences in xenobiotic metabolism and activation of carcinogen.

    PubMed Central

    Lewis, D F; Ioannides, C; Parke, D V

    1998-01-01

    The importance of cytochrome P450 isoforms to species differences in the metabolism of foreign compounds and activation of procarcinogens has been identified. The possible range of P450 isozymes in significant variations in toxicity exhibited by experimental rodent species may have a relevance to chemical risk assessment, especially as human P450s are likely to show changes in the way they metabolize xenobiotics. Consequently, in the safety evaluation of chemicals, we should be cautious in extrapolating results from experimental animal models to humans. This paper focuses on examples in which species differences in P450s lead to significant alterations in carcinogenic response, and includes a discussion of the current procedures for toxicity screening, with an emphasis on short-term tests. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:9755138

  16. Chronic inhibition of 11 β -hydroxysteroid dehydrogenase type 1 activity decreases hypertension, insulin resistance, and hypertriglyceridemia in metabolic syndrome.

    PubMed

    Schnackenberg, Christine G; Costell, Melissa H; Krosky, Daniel J; Cui, Jianqi; Wu, Charlene W; Hong, Victor S; Harpel, Mark R; Willette, Robert N; Yue, Tian-Li

    2013-01-01

    Metabolic syndrome is a constellation of risk factors including hypertension, dyslipidemia, insulin resistance, and obesity that promote the development of cardiovascular disease. Metabolic syndrome has been associated with changes in the secretion or metabolism of glucocorticoids, which have important functions in adipose, liver, kidney, and vasculature. Tissue concentrations of the active glucocorticoid cortisol are controlled by the conversion of cortisone to cortisol by 11 β -hydroxysteroid dehydrogenase type 1 (11 β -HSD1). Because of the various cardiovascular and metabolic activities of glucocorticoids, we tested the hypothesis that 11 β -HSD1 is a common mechanism in the hypertension, dyslipidemia, and insulin resistance in metabolic syndrome. In obese and lean SHR/NDmcr-cp (SHR-cp), cardiovascular, metabolic, and renal functions were measured before and during four weeks of administration of vehicle or compound 11 (10 mg/kg/d), a selective inhibitor of 11 β -HSD1. Compound 11 significantly decreased 11 β -HSD1 activity in adipose tissue and liver of SHR-cp. In obese SHR-cp, compound 11 significantly decreased mean arterial pressure, glucose intolerance, insulin resistance, hypertriglyceridemia, and plasma renin activity with no effect on heart rate, body weight gain, or microalbuminuria. These results suggest that 11 β -HSD1 activity in liver and adipose tissue is a common mediator of hypertension, hypertriglyceridemia, glucose intolerance, and insulin resistance in metabolic syndrome.

  17. Chronic Inhibition of 11β-Hydroxysteroid Dehydrogenase Type 1 Activity Decreases Hypertension, Insulin Resistance, and Hypertriglyceridemia in Metabolic Syndrome

    PubMed Central

    Schnackenberg, Christine G.; Costell, Melissa H.; Krosky, Daniel J.; Cui, Jianqi; Wu, Charlene W.; Hong, Victor S.; Harpel, Mark R.; Willette, Robert N.; Yue, Tian-Li

    2013-01-01

    Metabolic syndrome is a constellation of risk factors including hypertension, dyslipidemia, insulin resistance, and obesity that promote the development of cardiovascular disease. Metabolic syndrome has been associated with changes in the secretion or metabolism of glucocorticoids, which have important functions in adipose, liver, kidney, and vasculature. Tissue concentrations of the active glucocorticoid cortisol are controlled by the conversion of cortisone to cortisol by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Because of the various cardiovascular and metabolic activities of glucocorticoids, we tested the hypothesis that 11β-HSD1 is a common mechanism in the hypertension, dyslipidemia, and insulin resistance in metabolic syndrome. In obese and lean SHR/NDmcr-cp (SHR-cp), cardiovascular, metabolic, and renal functions were measured before and during four weeks of administration of vehicle or compound 11 (10 mg/kg/d), a selective inhibitor of 11β-HSD1. Compound 11 significantly decreased 11β-HSD1 activity in adipose tissue and liver of SHR-cp. In obese SHR-cp, compound 11 significantly decreased mean arterial pressure, glucose intolerance, insulin resistance, hypertriglyceridemia, and plasma renin activity with no effect on heart rate, body weight gain, or microalbuminuria. These results suggest that 11β-HSD1 activity in liver and adipose tissue is a common mediator of hypertension, hypertriglyceridemia, glucose intolerance, and insulin resistance in metabolic syndrome. PMID:23586038

  18. Oxygen Affects Gut Bacterial Colonization and Metabolic Activities in a Gnotobiotic Cockroach Model

    PubMed Central

    Tegtmeier, Dorothee; Thompson, Claire L.; Schauer, Christine

    2015-01-01

    The gut microbiota of termites and cockroaches represents complex metabolic networks of many diverse microbial populations. The distinct microenvironmental conditions within the gut and possible interactions among the microorganisms make it essential to investigate how far the metabolic properties of pure cultures reflect their activities in their natural environment. We established the cockroach Shelfordella lateralis as a gnotobiotic model and inoculated germfree nymphs with two bacterial strains isolated from the guts of conventional cockroaches. Fluorescence microscopy revealed that both strains specifically colonized the germfree hindgut. In diassociated cockroaches, the facultatively anaerobic strain EbSL (a new species of Enterobacteriaceae) always outnumbered the obligately anaerobic strain FuSL (a close relative of Fusobacterium varium), irrespective of the sequence of inoculation, which showed that precolonization by facultatively anaerobic bacteria does not necessarily favor colonization by obligate anaerobes. Comparison of the fermentation products of the cultures formed in vitro with those accumulated in situ indicated that the gut environment strongly affected the metabolic activities of both strains. The pure cultures formed the typical products of mixed-acid or butyrate fermentation, whereas the guts of gnotobiotic cockroaches accumulated mostly lactate and acetate. Similar shifts toward more-oxidized products were observed when the pure cultures were exposed to oxygen, which corroborated the strong effects of oxygen on the metabolic fluxes previously observed in termite guts. Oxygen microsensor profiles of the guts of germfree, gnotobiotic, and conventional cockroaches indicated that both gut tissue and microbiota contribute to oxygen consumption and suggest that the oxygen status influences the colonization success. PMID:26637604

  19. Oxygen Affects Gut Bacterial Colonization and Metabolic Activities in a Gnotobiotic Cockroach Model.

    PubMed

    Tegtmeier, Dorothee; Thompson, Claire L; Schauer, Christine; Brune, Andreas

    2016-02-01

    The gut microbiota of termites and cockroaches represents complex metabolic networks of many diverse microbial populations. The distinct microenvironmental conditions within the gut and possible interactions among the microorganisms make it essential to investigate how far the metabolic properties of pure cultures reflect their activities in their natural environment. We established the cockroach Shelfordella lateralis as a gnotobiotic model and inoculated germfree nymphs with two bacterial strains isolated from the guts of conventional cockroaches. Fluorescence microscopy revealed that both strains specifically colonized the germfree hindgut. In diassociated cockroaches, the facultatively anaerobic strain EbSL (a new species of Enterobacteriaceae) always outnumbered the obligately anaerobic strain FuSL (a close relative of Fusobacterium varium), irrespective of the sequence of inoculation, which showed that precolonization by facultatively anaerobic bacteria does not necessarily favor colonization by obligate anaerobes. Comparison of the fermentation products of the cultures formed in vitro with those accumulated in situ indicated that the gut environment strongly affected the metabolic activities of both strains. The pure cultures formed the typical products of mixed-acid or butyrate fermentation, whereas the guts of gnotobiotic cockroaches accumulated mostly lactate and acetate. Similar shifts toward more-oxidized products were observed when the pure cultures were exposed to oxygen, which corroborated the strong effects of oxygen on the metabolic fluxes previously observed in termite guts. Oxygen microsensor profiles of the guts of germfree, gnotobiotic, and conventional cockroaches indicated that both gut tissue and microbiota contribute to oxygen consumption and suggest that the oxygen status influences the colonization success. PMID:26637604

  20. Oxygen Affects Gut Bacterial Colonization and Metabolic Activities in a Gnotobiotic Cockroach Model.

    PubMed

    Tegtmeier, Dorothee; Thompson, Claire L; Schauer, Christine; Brune, Andreas

    2015-12-04

    The gut microbiota of termites and cockroaches represents complex metabolic networks of many diverse microbial populations. The distinct microenvironmental conditions within the gut and possible interactions among the microorganisms make it essential to investigate how far the metabolic properties of pure cultures reflect their activities in their natural environment. We established the cockroach Shelfordella lateralis as a gnotobiotic model and inoculated germfree nymphs with two bacterial strains isolated from the guts of conventional cockroaches. Fluorescence microscopy revealed that both strains specifically colonized the germfree hindgut. In diassociated cockroaches, the facultatively anaerobic strain EbSL (a new species of Enterobacteriaceae) always outnumbered the obligately anaerobic strain FuSL (a close relative of Fusobacterium varium), irrespective of the sequence of inoculation, which showed that precolonization by facultatively anaerobic bacteria does not necessarily favor colonization by obligate anaerobes. Comparison of the fermentation products of the cultures formed in vitro with those accumulated in situ indicated that the gut environment strongly affected the metabolic activities of both strains. The pure cultures formed the typical products of mixed-acid or butyrate fermentation, whereas the guts of gnotobiotic cockroaches accumulated mostly lactate and acetate. Similar shifts toward more-oxidized products were observed when the pure cultures were exposed to oxygen, which corroborated the strong effects of oxygen on the metabolic fluxes previously observed in termite guts. Oxygen microsensor profiles of the guts of germfree, gnotobiotic, and conventional cockroaches indicated that both gut tissue and microbiota contribute to oxygen consumption and suggest that the oxygen status influences the colonization success.

  1. Non-Invasive Microbial Metabolic Activity Sensing at Single Cell Level by Perfusion of Calcein Acetoxymethyl Ester

    PubMed Central

    Krämer, Christina E. M.; Singh, Abhijeet; Helfrich, Stefan; Grünberger, Alexander; Wiechert, Wolfgang; Nöh, Katharina; Kohlheyer, Dietrich

    2015-01-01

    Phase contrast microscopy cannot give sufficient information on bacterial metabolic activity, or if a cell is dead, it has the fate to die or it is in a viable but non-growing state. Thus, a reliable sensing of the metabolic activity helps to distinguish different categories of viability. We present a non-invasive instantaneous sensing method using a fluorogenic substrate for online monitoring of esterase activity and calcein efflux changes in growing wild type bacteria. The fluorescent conversion product of calcein acetoxymethyl ester (CAM) and its efflux indicates the metabolic activity of cells grown under different conditions at real-time. The dynamic conversion of CAM and the active efflux of fluorescent calcein were analyzed by combining microfluidic single cell cultivation technology and fluorescence time lapse microscopy. Thus, an instantaneous and non-invasive sensing method for apparent esterase activity was created without the requirement of genetic modification or harmful procedures. The metabolic activity sensing method consisting of esterase activity and calcein secretion was demonstrated in two applications. Firstly, growing colonies of our model organism Corynebacterium glutamicum were confronted with intermittent nutrient starvation by interrupting the supply of iron and carbon, respectively. Secondly, bacteria were exposed for one hour to fatal concentrations of antibiotics. Bacteria could be distinguished in growing and non-growing cells with metabolic activity as well as non-growing and non-fluorescent cells with no detectable esterase activity. Microfluidic single cell cultivation combined with high temporal resolution time-lapse microscopy facilitated monitoring metabolic activity of stressed cells and analyzing their descendants in the subsequent recovery phase. Results clearly show that the combination of CAM with a sampling free microfluidic approach is a powerful tool to gain insights in the metabolic activity of growing and non

  2. Analysis of drug metabolism activities in a miniaturized liver cell bioreactor for use in pharmacological studies.

    PubMed

    Hoffmann, Stefan A; Müller-Vieira, Ursula; Biemel, Klaus; Knobeloch, Daniel; Heydel, Sandra; Lübberstedt, Marc; Nüssler, Andreas K; Andersson, Tommy B; Gerlach, Jörg C; Zeilinger, Katrin

    2012-12-01

    Based on a hollow fiber perfusion technology with internal oxygenation, a miniaturized bioreactor with a volume of 0.5 mL for in vitro studies was recently developed. Here, the suitability of this novel culture system for pharmacological studies was investigated, focusing on the model drug diclofenac. Primary human liver cells were cultivated in bioreactors and in conventional monolayer cultures in parallel over 10 days. From day 3 on, diclofenac was continuously applied at a therapeutic concentration (6.4 µM) for analysis of its metabolism. In addition, the activity and gene expression of the cytochrome P450 (CYP) isoforms CYP1A2, CYP2B6, CYP2C9, CYP2D6, and CYP3A4 were assessed. Diclofenac was metabolized in bioreactor cultures with an initial conversion rate of 230 ± 57 pmol/h/10(6) cells followed by a period of stable conversion of about 100 pmol/h/10(6) cells. All CYP activities tested were maintained until day 10 of bioreactor culture. The expression of corresponding mRNAs correlated well with the degree of preservation. Immunohistochemical characterization showed the formation of neo-tissue with expression of CYP2C9 and CYP3A4 and the drug transporters breast cancer resistance protein (BCRP) and multidrug resistance protein 2 (MRP2) in the bioreactor. In contrast, monolayer cultures showed a rapid decline of diclofenac conversion and cells had largely lost activity and mRNA expression of the assessed CYP isoforms at the end of the culture period. In conclusion, diclofenac metabolism, CYP activities and gene expression levels were considerably more stable in bioreactor cultures, making the novel bioreactor a useful tool for pharmacological or toxicological investigations requiring a highly physiological in vitro representation of the liver.

  3. Regulation of bacterial metabolic activity by dissolved organic carbon and viruses

    NASA Astrophysics Data System (ADS)

    Xu, Jie; Jing, Hongmei; Sun, Mingming; Harrison, Paul J.; Liu, Hongbin

    2013-12-01

    regulation of bacterial metabolic activity by viruses and dissolved organic carbon (DOC) was examined using natural microbial communities in three treatments (active viruses, inactive viruses, and virus free) at two contrasting coastal sites (pristine vs. eutrophic) with substantial differences in environmental conditions during the wet and dry seasons. Our results showed that net growth rates and production of bacterioplankton were reduced primarily by viruses via repressing metabolically active bacteria with high nucleic acid (HNA) content which had a high capacity for incorporating carbon, while bacterial respiration was primarily regulated by DOC lability. The quality of organic matter played a more important role in regulating bacterial growth efficiency (BGE) than the supply of organic matter in eutrophic coastal waters. The lack of HMW-DOC and high carbon demand in the virus-free treatment resulted in a significant increase in cell-specific bacterial respiration, which was responsible for the lowest bacterial growth efficiency among the three treatments. The presence of viruses did not necessarily lower bacterial growth efficiency since virus-induced mortality alleviated bacterial carbon demand and enhanced carbon cycling. Virus-induced mortality was greater in relatively pristine waters than eutrophic waters, likely since the high supply of substrates alleviated the pressure of viral infection, through extracellular proteases produced by bacteria, which might result in the hydrolytic destruction or modification of viral capsids. An important implication of our results was that the input of riverine DOC and nutrients improved bacterial metabolic activity by alleviating virus-induced mortality of bacteria in estuarine and coastal waters.

  4. Relevance of drug metabolizing enzyme activity modulation by tea polyphenols in the inhibition of esophageal tumorigenesis.

    PubMed

    Maliakal, Pius; Sankpal, Umesh T; Basha, Riyaz; Maliakal, Cima; Ledford, Andrea; Wanwimolruk, Sompon

    2011-09-01

    Tea is a popular, socially accepted, drink that is enjoyed by millions of people. A growing body of evidence suggests that moderate consumption of tea may protect against several forms of cancer. It is also known that bioactivation of precarcinogens and detoxification of ultimate carcinogens is carried out mainly by drug metabolizing enzymes such as cytochrome P450 (CYP). The present study investigates the effect of tea consumption on modulating CYP and phase II conjugating enzymes, and their association in the chemopreventive effect against esophageal tumorigenesis using both in vitro and in vivo techniques. Female Wistar rats were given aqueous solutions (2% w/v) of six different teas, standard green tea extract (GTE) (0.5% w/v), and dandelion tea (2% w/v) as the sole source of fluid for two weeks prior to and during the entire period of tumour induction (12 weeks). Animals were gavaged with 0.5 mg/kg N-nitrosomethylbenzylamine (NMBA) twice weekly for 12 weeks for esophageal tumor induction and the activities of different CYP isoforms and phase II enzymes were determined in the liver microsomes or cytosols. GTE, green tea and Dandelion tea caused decrease in tumour multiplication, tumour size and tumour volume; however, none of these tea preparations altered tumour incidence. No appreciable changes in drug metabolizing enzyme activity were observed in the treatment groups. Thus, the modulations in the activities of CYP 1A1/ 1A2 and CYP2E enzymes, by pre-treatment with green and dandelion teas, observed in our earlier experiments, seem to be compensated by the tumor inducing agent, NMBA. The balance between phase I carcinogen-activating enzymes and phase II detoxifying enzymes could be important in determining the risk of developing chemically-induced cancer and the present study in conjunction with the previous observations suggest a possible role of drug metabolizing enzymes in the anticancer effect of tea.

  5. Modulation of fructokinase activity of potato (Solanum tuberosum) results in substantial shifts in tuber metabolism.

    PubMed

    Davies, Howard V; Shepherd, Louise V T; Burrell, Michael M; Carrari, Fernando; Urbanczyk-Wochniak, Ewa; Leisse, Andrea; Hancock, Robert D; Taylor, Mark; Viola, Roberto; Ross, Heather; McRae, Diane; Willmitzer, Lothar; Fernie, Alisdair R

    2005-07-01

    Potato plants (Solanum tuberosum L. cvs Desiree and Record) transformed with sense and antisense constructs of a cDNA encoding the potato fructokinase StFK1 exhibited altered transcription of this gene, altered amount of protein and altered enzyme activities. Measurement of the maximal catalytic activity of fructokinase revealed a 2-fold variation in leaf (from 90 to 180% of wild type activity) and either a 10- or 30-fold variation in tuber (from 10 or 30% to 300% in Record and Desiree, respectively) activity. The comparative effect of the antisense construct in leaf and tuber tissue suggests that this isoform is only a minor contributor to the total fructokinase activity in the leaf but the predominant isoform in the tuber. Antisense inhibition of the fructokinase resulted in a reduced tuber yield; however, its overexpression had no impact on this parameter. The modulation of fructokinase activity had few, consistent effects on carbohydrate levels, with the exception of a general increase in glucose content in the antisense lines, suggesting that this enzyme is not important for the control of starch synthesis. However, when metabolic fluxes were estimated, it became apparent that the transgenic lines display a marked shift in metabolism, with the rate of redistribution of radiolabel to sucrose markedly affected by the activity of fructokinase. These data suggest an important role for fructokinase, acting in concert with sucrose synthase, in maintaining a balance between sucrose synthesis and degradation by a mechanism independent of that controlled by the hexose phosphate-mediated activation of sucrose phosphate synthase. PMID:15890680

  6. Modulation of fructokinase activity of potato (Solanum tuberosum) results in substantial shifts in tuber metabolism.

    PubMed

    Davies, Howard V; Shepherd, Louise V T; Burrell, Michael M; Carrari, Fernando; Urbanczyk-Wochniak, Ewa; Leisse, Andrea; Hancock, Robert D; Taylor, Mark; Viola, Roberto; Ross, Heather; McRae, Diane; Willmitzer, Lothar; Fernie, Alisdair R

    2005-07-01

    Potato plants (Solanum tuberosum L. cvs Desiree and Record) transformed with sense and antisense constructs of a cDNA encoding the potato fructokinase StFK1 exhibited altered transcription of this gene, altered amount of protein and altered enzyme activities. Measurement of the maximal catalytic activity of fructokinase revealed a 2-fold variation in leaf (from 90 to 180% of wild type activity) and either a 10- or 30-fold variation in tuber (from 10 or 30% to 300% in Record and Desiree, respectively) activity. The comparative effect of the antisense construct in leaf and tuber tissue suggests that this isoform is only a minor contributor to the total fructokinase activity in the leaf but the predominant isoform in the tuber. Antisense inhibition of the fructokinase resulted in a reduced tuber yield; however, its overexpression had no impact on this parameter. The modulation of fructokinase activity had few, consistent effects on carbohydrate levels, with the exception of a general increase in glucose content in the antisense lines, suggesting that this enzyme is not important for the control of starch synthesis. However, when metabolic fluxes were estimated, it became apparent that the transgenic lines display a marked shift in metabolism, with the rate of redistribution of radiolabel to sucrose markedly affected by the activity of fructokinase. These data suggest an important role for fructokinase, acting in concert with sucrose synthase, in maintaining a balance between sucrose synthesis and degradation by a mechanism independent of that controlled by the hexose phosphate-mediated activation of sucrose phosphate synthase.

  7. Metabolic syndrome, platelet activation and the development of transient ischemic attack or thromboembolic stroke.

    PubMed

    van Rooy, Mia-Jeanne; Pretorius, Etheresia

    2015-03-01

    Stroke is the second most common cause of mortality in the world today, where transient ischemic attack (TIA) is a period of focal ischemia, the symptoms of which resemble a thromboembolic stroke. Contrary to stroke, TIA symptoms typically last less than one hour and necrosis is absent. Stroke is often preceded by TIA, making it an important predictor of future ischemic events. The causal role of atherosclerosis in the development of TIA is well established, however, research indicates that the atherosclerotic process begins years earlier with the development of metabolic syndrome, which affects approximately 45% of the adult population worldwide. Metabolic syndrome is present if three or more of the following is present: increased waist circumference, increased triglycerides, decreased HDL, increased fasting glucose and hypertension. This syndrome causes systemic inflammation that activates the coagulation system and may cause the formation of pathological thrombi. The role of platelets in stroke has been studied and platelet activation pathways identified. ADP and thromboxane A(2) are the most common activators of platelets in normal physiology. Several pharmacological treatments have been employed to prevent the activation of platelets, the most common of which include aspirin and P2Y(12)-inhibitors. Although treatment is administered strokes and subsequent TIAs are very common in individuals that suffered an initial event. This indicates that research needs to be done in order to elucidate new therapeutic targets, but also to better treat ischemic events to not only decrease the amount of recurring events but also decrease stroke mortality worldwide.

  8. The influence of carbon dioxide on brain activity and metabolism in conscious humans

    PubMed Central

    Xu, Feng; Uh, Jinsoo; Brier, Matthew R; Hart, John; Yezhuvath, Uma S; Gu, Hong; Yang, Yihong; Lu, Hanzhang

    2011-01-01

    A better understanding of carbon dioxide (CO2) effect on brain activity may have a profound impact on clinical studies using CO2 manipulation to assess cerebrovascular reserve and on the use of hypercapnia as a means to calibrate functional magnetic resonance imaging (fMRI) signal. This study investigates how an increase in blood CO2, via inhalation of 5% CO2, may alter brain activity in humans. Dynamic measurement of brain metabolism revealed that mild hypercapnia resulted in a suppression of cerebral metabolic rate of oxygen (CMRO2) by 13.4%±2.3% (N=14) and, furthermore, the CMRO2 change was proportional to the subject's end-tidal CO2 (Et-CO2) change. When using functional connectivity MRI (fcMRI) to assess the changes in resting-state neural activity, it was found that hypercapnia resulted in a reduction in all fcMRI indices assessed including cluster volume, cross-correlation coefficient, and amplitude of the fcMRI signal in the default-mode network (DMN). The extent of the reduction was more pronounced than similar indices obtained in visual-evoked fMRI, suggesting a selective suppression effect on resting-state neural activity. Scalp electroencephalogram (EEG) studies comparing hypercapnia with normocapnia conditions showed a relative increase in low frequency power in the EEG spectra, suggesting that the brain is entering a low arousal state on CO2 inhalation. PMID:20842164

  9. Metabolic activity of moulds as a factor of building materials biodegradation.

    PubMed

    Gutarowska, Beata

    2010-01-01

    This paper presents the effect of building materials on the growth and metabolic activity of moulds. In cultures of Aspergillus and Penicillium moulds grown on a model medium with the addition of building materials, the biomass of mycelium, its cellular components--glucan, chitin, ergosterol and the spectrum of enzymes and organic acids produced in the medium were investigated. It was found that on the medium with wallpaper moulds produced more biomass and extracellular enzymes, mainly glycolytic ones. On medium with mortar the growth of mycelium was impeded, production of biomass was 60% smaller, the quantity of chitin, glucan and ergosterol decreased 13-41%, and the activity of most enzymes was reduced; however the moulds intensively produced organic acids: malic, succinic and oxalic acid. The largest acid production activity was found in medium with addition of mortar; moulds produced the greatest variety of acids and in greater quantities than in the control medium. Metabolic activity of the moulds depends on the type of building material, and may lead to biodeterioration of these materials.

  10. Lactobacillus fermentum CRL1446 Ameliorates Oxidative and Metabolic Parameters by Increasing Intestinal Feruloyl Esterase Activity and Modulating Microbiota in Caloric-Restricted Mice

    PubMed Central

    Russo, Matias; Fabersani, Emanuel; Abeijón-Mukdsi, María C.; Ross, Romina; Fontana, Cecilia; Benítez-Páez, Alfonso; Gauffin-Cano, Paola; Medina, Roxana B.

    2016-01-01

    The purpose of this study was to determine whether the administration of the feruloyl esterase (FE)-producing strain Lactobacillus fermentum CRL1446 enhances metabolic and oxidative parameters in caloric-restricted (CR) mice. Balb/c male mice were divided into ad libitum fed Group (ALF Group), CR diet Group (CR Group) and CR diet plus L. fermentum Group (CR-Lf Group). CR diet was administered during 45 days and CRL1446 strain was given in the dose of 108 cells/mL/day/mouse. FE activity was determined in intestinal mucosa and content at Day 1, 20 and 45. Triglyceride, total cholesterol, glucose, thiobarbituric acid reactive substances (TBARS) levels and glutathione reductase activity were determined in plasma. Gut microbiota was evaluated by high-throughput sequencing of 16S rRNA gene amplicons. At Day 45, total intestinal FE activity in CR-Lf Group was higher (p = 0.020) than in CR and ALF groups and an improvement in both metabolic (reductions in triglyceride (p = 0.0025), total cholesterol (p = 0.005) and glucose (p < 0.0001) levels) and oxidative (decrease of TBARS levels and increase of plasmatic glutathione reductase activity (p = 0.006)) parameters was observed, compared to ALF Group. CR diet increased abundance of Bacteroidetes and CRL1446 administration increased abundance of Bifidobacterium and Lactobacillus genus. L. fermentun CRL1446 exerted a bifidogenic effect under CR conditions. PMID:27399766

  11. Lactobacillus fermentum CRL1446 Ameliorates Oxidative and Metabolic Parameters by Increasing Intestinal Feruloyl Esterase Activity and Modulating Microbiota in Caloric-Restricted Mice.

    PubMed

    Russo, Matias; Fabersani, Emanuel; Abeijón-Mukdsi, María C; Ross, Romina; Fontana, Cecilia; Benítez-Páez, Alfonso; Gauffin-Cano, Paola; Medina, Roxana B

    2016-01-01

    The purpose of this study was to determine whether the administration of the feruloyl esterase (FE)-producing strain Lactobacillus fermentum CRL1446 enhances metabolic and oxidative parameters in caloric-restricted (CR) mice. Balb/c male mice were divided into ad libitum fed Group (ALF Group), CR diet Group (CR Group) and CR diet plus L. fermentum Group (CR-Lf Group). CR diet was administered during 45 days and CRL1446 strain was given in the dose of 10⁸ cells/mL/day/mouse. FE activity was determined in intestinal mucosa and content at Day 1, 20 and 45. Triglyceride, total cholesterol, glucose, thiobarbituric acid reactive substances (TBARS) levels and glutathione reductase activity were determined in plasma. Gut microbiota was evaluated by high-throughput sequencing of 16S rRNA gene amplicons. At Day 45, total intestinal FE activity in CR-Lf Group was higher (p = 0.020) than in CR and ALF groups and an improvement in both metabolic (reductions in triglyceride (p = 0.0025), total cholesterol (p = 0.005) and glucose (p < 0.0001) levels) and oxidative (decrease of TBARS levels and increase of plasmatic glutathione reductase activity (p = 0.006)) parameters was observed, compared to ALF Group. CR diet increased abundance of Bacteroidetes and CRL1446 administration increased abundance of Bifidobacterium and Lactobacillus genus. L. fermentun CRL1446 exerted a bifidogenic effect under CR conditions. PMID:27399766

  12. A combination of molecular dynamics and docking calculations to explore the binding mode of ADS-J1, a polyanionic compound endowed with anti-HIV-1 activity.

    PubMed

    Manetti, Fabrizio; Tintori, Cristina; Armand-Ugón, Mercedes; Clotet-Codina, Imma; Massa, Silvio; Ragno, Rino; Esté, José A; Botta, Maurizio

    2006-01-01

    The HIV-1 entry process is an important target for the design of new pharmaceuticals for the multidrug therapy of AIDS. A lot of polyanionic compounds, such as polysulfonated and polysulfated, are reported in the literature for their ability to block early stages of HIV-1 replication. Several studies have been performed to elucidate the mechanism of the anti-HIV-1 activity of sulfated polysaccharides and polyanions in general, including binding to cell surface CD4 and interfering with the gp120-coreceptor interaction. Here, we show molecular modeling investigations on ADS-J1, a polyanionic compound with anti-HIV activity that is able to interfere with gp120-coreceptor interactions. Agreeing with experimental data, computer simulations suggested that the V3 loop of gp120 was the preferential binding site for ADS-J1 onto HIV-1. Moreover, mutations induced by the inhibitor significantly changed the stereoelectronic properties of the gp120 surface, justifying a marked drop in the affinity of ADS-J1 toward an ADS-J1-resistant HIV-1 strain.

  13. Recommended Levels of Physical Activity Are Associated with Reduced Risk of the Metabolic Syndrome in Mexican-Americans

    PubMed Central

    Wu, Shenghui; Fisher-Hoch, Susan P.; Reininger, Belinda; McCormick, Joseph B.

    2016-01-01

    Purpose To measure the association between physical activity and the metabolic syndrome risk in Mexican-Americans. Methods Participants were drawn from the Cameron County Hispanic Cohort (n = 3,414), a randomly selected Mexican-American cohort in Texas on the US-Mexico border. Moderate and vigorous physical activity was assessed using reliable and validated instruments. The metabolic syndrome was defined as having 3 or more metabolic abnormalities. Results One thousand five hundred and twenty-four participants of the cohort (45.02%) were found to have the metabolic syndrome. Compared to participants who did not meet US physical activity guidelines, participants who met physical activity guidelines of 150 moderate and vigorous minutes per week (≥ 600 MET adjusted minutes) had 36% lower risk for the metabolic syndrome (OR = 0.64; 95% CI: 0.42–0.98), and participants with total minutes per week of moderate and vigorous/strenuous activity greater than 743 MET adjusted minutes had 37% lower risk for the metabolic syndrome (OR = 0.63; 95% CI: 0.42–0.94) compared with their counterparts, after adjusting for age, gender, annual household income, body mass index, smoking and alcohol drinking status, total portions of fruit and vegetable intake, census tracts and blocks, and survey version for physical activity. Conclusions Meeting or exceeding physical activity guidelines significantly was inversely associated with the risk for the metabolic syndrome in Mexican-Americans. Improving levels of physical activity appears to be an effective target for the metabolic syndrome prevention and control among Mexican-Americans independent of other factors. PMID:27054324

  14. Tomato responds to green peach aphid infestation with the activation of trehalose metabolism and starch accumulation.

    PubMed

    Singh, Vijay; Shah, Jyoti

    2012-06-01

    The disaccharide trehalose and trehalose-6-phosphate that are present in trace amounts are suggested to have a signaling function in plants. Recently, it was demonstrated that trehalose metabolism contributes to Arabidopsis thaliana defense against the green peach aphid (GPA; Myzus persicae Sülzer), an important insect pest of a large variety of plants. TPS11 (TREHALOSE PHOSPHATE SYNTHASE11)-dependent trehalose metabolism was shown to curtail GPA infestation by promoting starch accumulation and expression of the PAD4 (PHYTOALEXIN-DEFICIENT4) gene, which has important roles in regulating antibiosis and antixenosis against GPA. Here we show that trehalose metabolism is similarly activated in leaves of GPA-infested tomato (Solanum lycopersicum) plants and likely contributes to tomato defense against GPA. GPA-infested leaves of tomato accumulated trehalose, which was accompanied by the transient upregulation of SlTPS11, a homolog of the Arabidopsis TPS11. GPA-infestation was also accompanied by starch accumulation and the upregulation of SlPAD4, the tomato homolog of Arabidopsis PAD4. Furthermore, trehalose application induced SlPAD4 expression and starch accumulation, and curtailed GPA infestation, suggesting that like in Arabidopsis trehalose contributes to tomato defense against GPA.

  15. Adenosine, Ketogenic Diet and Epilepsy: The Emerging Therapeutic Relationship Between Metabolism and Brain Activity

    PubMed Central

    Masino, S.A; Kawamura, M; Wasser, C.D.; Pomeroy, L.T; Ruskin, D.N

    2009-01-01

    For many years the neuromodulator adenosine has been recognized as an endogenous anticonvulsant molecule and termed a “retaliatory metabolite.” As the core molecule of ATP, adenosine forms a unique link between cell energy and neuronal excitability. In parallel, a ketogenic (high-fat, low-carbohydrate) diet is a metabolic therapy that influences neuronal activity significantly, and ketogenic diets have been used successfully to treat medically-refractory epilepsy, particularly in children, for decades. To date the key neural mechanisms underlying the success of dietary therapy are unclear, hindering development of analogous pharmacological solutions. Similarly, adenosine receptor–based therapies for epilepsy and myriad other disorders remain elusive. In this review we explore the physiological regulation of adenosine as an anticonvulsant strategy and suggest a critical role for adenosine in the success of ketogenic diet therapy for epilepsy. While the current focus is on the regulation of adenosine, ketogenic metabolism and epilepsy, the therapeutic implications extend to acute and chronic neurological disorders as diverse as brain injury, inflammatory and neuropathic pain, autism and hyperdopaminergic disorders. Emerging evidence for broad clinical relevance of the metabolic regulation of adenosine will be discussed. PMID:20190967

  16. Adenosine, ketogenic diet and epilepsy: the emerging therapeutic relationship between metabolism and brain activity.

    PubMed

    Masino, S A; Kawamura, M; Wasser, C D; Wasser, C A; Pomeroy, L T; Ruskin, D N

    2009-09-01

    For many years the neuromodulator adenosine has been recognized as an endogenous anticonvulsant molecule and termed a "retaliatory metabolite." As the core molecule of ATP, adenosine forms a unique link between cell energy and neuronal excitability. In parallel, a ketogenic (high-fat, low-carbohydrate) diet is a metabolic therapy that influences neuronal activity significantly, and ketogenic diets have been used successfully to treat medically-refractory epilepsy, particularly in children, for decades. To date the key neural mechanisms underlying the success of dietary therapy are unclear, hindering development of analogous pharmacological solutions. Similarly, adenosine receptor-based therapies for epilepsy and myriad other disorders remain elusive. In this review we explore the physiological regulation of adenosine as an anticonvulsant strategy and suggest a critical role for adenosine in the success of ketogenic diet therapy for epilepsy. While the current focus is on the regulation of adenosine, ketogenic metabolism and epilepsy, the therapeutic implications extend to acute and chronic neurological disorders as diverse as brain injury, inflammatory and neuropathic pain, autism and hyperdopaminergic disorders. Emerging evidence for broad clinical relevance of the metabolic regulation of adenosine will be discussed. PMID:20190967

  17. Metabolic Profiles and Free Radical Scavenging Activity of Cordyceps bassiana Fruiting Bodies According to Developmental Stage

    PubMed Central

    Hyun, Sun-Hee; Lee, Seok-Young; Sung, Gi-Ho; Kim, Seong Hwan; Choi, Hyung-Kyoon

    2013-01-01

    The metabolic profiles of Cordyceps bassiana according to fruiting body developmental stage were investigated using gas chromatography-mass spectrometry. We were able to detect 62 metabolites, including 48 metabolites from 70% methanol extracts and 14 metabolites from 100% n-hexane extracts. These metabolites were classified as alcohols, amino acids, organic acids, phosphoric acids, purine nucleosides and bases, sugars, saturated fatty acids, unsaturated fatty acids, or fatty amides. Significant changes in metabolite levels were found according to developmental stage. Relative levels of amino acids, purine nucleosides, and sugars were higher in development stage 3 than in the other stages. Among the amino acids, valine, isoleucine, lysine, histidine, glutamine, and aspartic acid, which are associated with ABC transporters and aminoacyl-tRNA biosynthesis, also showed higher levels in stage 3 samples. The free radical scavenging activities, which were significantly higher in stage 3 than in the other stages, showed a positive correlation with purine nucleoside metabolites such as adenosine, guanosine, and inosine. These results not only show metabolic profiles, but also suggest the metabolic pathways associated with fruiting body development stages in cultivated C. bassiana. PMID:24058459

  18. Geographic differences in digoxin inactivation, a metabolic activity of the human anaerobic gut flora.

    PubMed Central

    Mathan, V I; Wiederman, J; Dobkin, J F; Lindenbaum, J

    1989-01-01

    The inactivation of digoxin by conversion to reduced metabolites (digoxin reduction products, or DRP), a function of the anaerobic gut flora, was studied in normal volunteers from southern India and the United States. Digoxin was metabolised to DRP by 28 (13.7%) of 204 healthy south Indians in contrast to 67 (36.0%) of 186 New Yorkers (p less than 1 X 10(-6)). Only 1.0% of Indians compared with 14.0% of Americans excreted large amounts of metabolites (greater than 40% DRP) in the urine (p less than 1 X 10(-5)). Of 104 urban Indians, 23 (22.1%) were metabolisers, in contrast with five of 100 rural villagers (p less than 0.001). Within the urban group, digoxin metabolism correlated with education, frequency of animal protein intake, and most significantly, personal income. Organisms capable of reducing digoxin in vitro were found with similar frequencies in stool cultures from Indians and Americans. In the cultures of some subjects, DRP production was inhibited at lower dilutions but expressed at higher dilutions. We conclude that variations in drug metabolism between population groups may result from differences in the metabolic activity of the anaerobic gut flora probably mediated by environmentally determined factors. PMID:2759492

  19. Ginsenoside Rf, a component of ginseng, regulates lipoprotein metabolism through peroxisome proliferator-activated receptor {alpha}

    SciTech Connect

    Lee, Hyunghee; Gonzalez, Frank J.; Yoon, Michung . E-mail: yoon60@mokwon.ac.kr

    2006-01-06

    We investigated whether ginseng regulates lipoprotein metabolism by altering peroxisome proliferator-activated receptor {alpha} (PPAR{alpha})-mediated pathways, using a PPAR{alpha}-null mouse model. Administration of ginseng extract, ginsenosides, and ginsenoside Rf (Rf) to wild-type mice not only significantly increased basal levels of hepatic apolipoprotein (apo) A-I and C-III mRNA compared with wild-type controls, but also substantially reversed the reductions in mRNA levels of apo A-I and C-III expected following treatment with the potent PPAR{alpha} ligand Wy14,643. In contrast, no effect was detected in the PPAR{alpha}-null mice. Testing of eight main ginsenosides on PPAR{alpha} reporter gene expression indicated that Rf was responsible for the effects of ginseng on lipoprotein metabolism. Furthermore, the inhibition of PPAR{alpha}-dependent transactivation by Rf seems to occur at the level of DNA binding. These results demonstrate that ginseng component Rf regulates apo A-I and C-III mRNA and the actions of Rf on lipoprotein metabolism are mediated via interactions with PPAR{alpha}.

  20. Metabolic reprogramming of alloantigen-activated T cells after hematopoietic cell transplantation

    PubMed Central

    Nguyen, Hung D.; Chatterjee, Shilpak; Haarberg, Kelley M.K.; Wu, Yongxia; Bastian, David; Heinrichs, Jessica; Fu, Jianing; Daenthanasanmak, Anusara; Schutt, Steven; Shrestha, Sharad; Liu, Chen; Wang, Honglin; Chi, Hongbo; Mehrotra, Shikhar

    2016-01-01

    Alloreactive donor T cells are the driving force in the induction of graft-versus-host disease (GVHD), yet little is known about T cell metabolism in response to alloantigens after hematopoietic cell transplantation (HCT). Here, we have demonstrated that donor T cells undergo metabolic reprograming after allogeneic HCT. Specifically, we employed a murine allogeneic BM transplant model and determined that T cells switch from fatty acid β-oxidation (FAO) and pyruvate oxidation via the tricarboxylic (TCA) cycle to aerobic glycolysis, thereby increasing dependence upon glutaminolysis and the pentose phosphate pathway. Glycolysis was required for optimal function of alloantigen-activated T cells and induction of GVHD, as inhibition of glycolysis by targeting mTORC1 or 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) ameliorated GVHD mortality and morbidity. Together, our results indicate that donor T cells use glycolysis as the predominant metabolic process after allogeneic HCT and suggest that glycolysis has potential as a therapeutic target for the control of GVHD. PMID:26950421

  1. Distribution of zooplankton biomass and potential metabolic activities across the northern Benguela upwelling system

    NASA Astrophysics Data System (ADS)

    Fernández-Urruzola, I.; Osma, N.; Packard, T. T.; Gómez, M.; Postel, L.

    2014-11-01

    The distribution of zooplankton biomass and potential metabolic rates, in terms of electron transport system (ETS) and glutamate dehydrogenase (GDH), were analyzed along a cross-shelf transect in waters off Namibia. The highly variable dynamics of upwelling filaments promoted short-term fluctuations in the zooplankton biomass and metabolism. Maximum values were characteristically found over the shelf-break, where zooplankton biomass as dry mass (DM) reached peaks of 64.5 mg m- 3 within the upper 200 m in late August. Two weeks later, the zooplankton-DM decreased by more than a third (19 mg DM m- 3). Zooplankton potential respiration and NH4+ excretion averaged 234 μmol O2 m- 3 d- 1 and 169 μmol NH4+ m- 3 d- 1 in the Namibian shelf, respectively. High protein-specific ETS activities even in the low-chlorophyll waters outside the filament suggested a shift into greater omnivory seaward. In this light, zooplankton elemental and isotopic compositions were used to investigate the pelagic food web interactions. They evidenced spatial changes in the carbon resource for zooplankton as well as changes in the form of nitrogen that fueled the biological production in aging advected waters. Overall, both aspects of zooplankton metabolism impacted the primary productivity at a level less than 10% under all the different oceanographic conditions.

  2. Composition and Metabolic Activities of Bacterial Biofilms Colonizing Food Residues in the Human Gut

    PubMed Central

    Macfarlane, Sandra; Macfarlane, George T.

    2006-01-01

    Bacteria growing in the human large intestine live in intimate association with the host and play an important role in host digestive processes, gut physiology, and metabolism. Fecal bacteria have been investigated extensively, but few studies have been done on biofilms that form on digestive wastes in the large bowel. The aims of this investigation were to investigate the composition and metabolic activities of bacterial communities that colonize the surfaces of food residues in fecal material, with respect to their role in the fermentation of complex carbohydrates. Fresh stools were obtained from 15 healthy donors, and food residues were separated by filtration. Adherent bacteria were removed by surfactant treatment for microbiological analysis and fermentation studies. Scanning electron microscopy and fluorescent in situ hybridization in conjunction with confocal laser scanning microscopy (CLSM) were used to visualize intact biofilms. Results showed that bacterial populations strongly adhering to particulate matter were phenotypically similar in composition to unattached communities, with bacteroides and bifidobacteria predominating. Biofilms comprised a mixture of living and dead bacteria, and CLSM showed that bifidobacteria in the biofilms occurred as isolated dispersed cells and in microcolonies near the interface with the substratum. Fermentation experiments with a variety of complex carbohydrates demonstrated that biofilm populations were more efficient in digesting polysaccharides, while nonadhering communities fermented oligosaccharides most rapidly. Acetate was the principal fermentation product formed by biofilm bacteria, whereas higher levels of butyrate were produced by nonadherent populations, showing that the two communities were metabolically distinct. PMID:16957247

  3. Combination of physical activity, nutrition, or other metabolic factors and vaccine response

    PubMed Central

    Hance, Kenneth W.; Rogers, Connie J.; Hursting, Stephen D.; Greiner, John W.

    2010-01-01

    A number of lifestyle factors that reduce cancer risk in the primary prevention setting may be potential new targets for use in combination with cancer vaccines. This review discusses the modulation of energy balance (physical activity, calorie restriction, and obesity prevention), and the supplementation with natural and synthetic analogs of vitamins A and E, as potential interventions for use in combination with cancer vaccines. Additionally, the pharmacologic manipulation of nutrient metabolism in the tumor microenvironment (e.g., arachidonic acid, arginine, tryptophan, and glucose metabolism) is discussed. This review includes a brief overview of the role of each agent in primary cancer prevention; outlines the effects of these agents on immune function, specifically adaptive and/or anti-tumor immune mechanisms, when known; and discusses the potential use of these interventions in combination with therapeutic cancer vaccines. Modulation of energy balance through exercise and strategies targeting nutrient metabolism in the tumor microenvironment represent the most promising interventions to partner with therapeutic cancer vaccines. Additionally, the use of vitamin E succinate and the retinoid X receptor-directed rexinoids in combination with cancer vaccines offer promise. In summary, a number of energy balance- and nutrition-related interventions are viable candidates for further study in combination with cancer vaccines. PMID:17569626

  4. Phytochemical Composition and Metabolic Performance Enhancing Activity of Dietary Berries Traditionally Used by Native North Americans

    PubMed Central

    Burns Kraft, Tristan F.; Dey, Moul; Rogers, Randy B.; Ribnicky, David M.; Gipp, David M.; Cefalu, William T.; Raskin, Ilya; Lila, Mary Ann

    2009-01-01

    Four wild berry species, Amelanchier alnifolia, Viburnum trilobum, Prunus virginiana, and Shepherdia argentea, all integral to the traditional subsistence diet of Native American tribal communities, were evaluated to elucidate phytochemical composition and bioactive properties related to performance and human health. Biological activity was screened using a range of bioassays that assessed the potential for these little-known dietary berries to affect diabetic microvascular complications, hyperglycemia, pro-inflammatory gene expression, and metabolic syndrome symptoms. Non-polar constituents from berries, including carotenoids, were potent inhibitors of aldose reductase (an enzyme involved in the etiology of diabetic microvascular complications) whereas the polar constituents, mainly phenolic acids, anthocyanins, and proanthocyanidins, were hypoglycemic agents and strong inhibitors of IL-1β and COX-2 gene expression. Berry samples also showed the ability to modulate lipid metabolism and energy expenditure in a manner consistent with improving metabolic syndrome. The results demonstrate that these berries traditionally consumed by tribal cultures contain a rich array of phytochemicals that have the capacity to promote health and protect against chronic diseases, such as diabetes. PMID:18211018

  5. Metabolic profiles and free radical scavenging activity of Cordyceps bassiana fruiting bodies according to developmental stage.

    PubMed

    Hyun, Sun-Hee; Lee, Seok-Young; Sung, Gi-Ho; Kim, Seong Hwan; Choi, Hyung-Kyoon

    2013-01-01

    The metabolic profiles of Cordyceps bassiana according to fruiting body developmental stage were investigated using gas chromatography-mass spectrometry. We were able to detect 62 metabolites, including 48 metabolites from 70% methanol extracts and 14 metabolites from 100% n-hexane extracts. These metabolites were classified as alcohols, amino acids, organic acids, phosphoric acids, purine nucleosides and bases, sugars, saturated fatty acids, unsaturated fatty acids, or fatty amides. Significant changes in metabolite levels were found according to developmental stage. Relative levels of amino acids, purine nucleosides, and sugars were higher in development stage 3 than in the other stages. Among the amino acids, valine, isoleucine, lysine, histidine, glutamine, and aspartic acid, which are associated with ABC transporters and aminoacyl-tRNA biosynthesis, also showed higher levels in stage 3 samples. The free radical scavenging activities, which were significantly higher in stage 3 than in the other stages, showed a positive correlation with purine nucleoside metabolites such as adenosine, guanosine, and inosine. These results not only show metabolic profiles, but also suggest the metabolic pathways associated with fruiting body development stages in cultivated C. bassiana.

  6. Acetylation of Werner syndrome protein (WRN): relationships with DNA damage, DNA replication and DNA metabolic activities

    PubMed Central

    Lozada, Enerlyn; Yi, Jingjie; Luo, Jianyuan; Orren, David K.

    2014-01-01

    Loss of WRN function causes Werner Syndrome, characterized by increased genomic instability, elevated cancer susceptibility and premature aging. Although WRN is subject to acetylation, phosphorylation and sumoylation, the impact of these modifications on WRN’s DNA metabolic function remains unclear. Here, we examined in further depth the relationship between WRN acetylation and its role in DNA metabolism, particularly in response to induced DNA damage. Our results demonstrate that endogenous WRN is acetylated somewhat under unperturbed conditions. However, levels of acetylated WRN significantly increase after treatment with certain DNA damaging agents or the replication inhibitor hydroxyurea. Use of DNA repair-deficient cells or repair pathway inhibitors further increase levels of acetylated WRN, indicating that induced DNA lesions and their persistence are at least partly responsible for increased acetylation. Notably, acetylation of WRN correlates with inhibition of DNA synthesis, suggesting that replication blockage might underlie this effect. Moreover, WRN acetylation modulates its affinity for and activity on certain DNA structures, in a manner that may enhance its relative specificity for physiological substrates. Our results also show that acetylation and deacetylation of endogenous WRN is a dynamic process, with sirtuins and other histone deacetylases contributing to WRN deacetylation. These findings advance our understanding of the dynamics of WRN acetylation under unperturbed conditions and following DNA damage induction, linking this modification not only to DNA damage persistence but also potentially to replication stalling caused by specific DNA lesions. Our results are consistent with proposed metabolic roles for WRN and genomic instability phenotypes associated with WRN deficiency. PMID:24965941

  7. Metabolomics Reveals that Aryl Hydrocarbon Receptor Activation by Environmental Chemicals Induces Systemic Metabolic Dysfunction in Mice

    PubMed Central

    Zhang, Limin; Hatzakis, Emmanuel; Nichols, Robert G.; Hao, Ruixin; Correll, Jared; Smith, Philip B.; Chiaro, Christopher R.; Perdew, Gary H.; Patterson, Andrew D.

    2016-01-01

    Environmental exposure to dioxins and dioxin-like compounds poses a significant health risk for human health. Developing a better understanding of the mechanisms of toxicity through activation of the aryl hydrocarbon receptor (AHR) is likely to improve the reliability of risk assessment. In this study, the AHR-dependent metabolic response of mice exposed to 2,3,7,8-tetrachlorodibenzofuran (TCDF) were assessed using global 1H nuclear magnetic resonance (NMR)-based metabolomics and targeted metabolic profiling of extracts obtained from serum and liver. 1H NMR analyses revealed that TCDF exposure suppressed gluconeogenesis and glycogenolysis, stimulated lipogenesis, and triggered inflammatory gene expression in an Ahr-dependent manner. Targeted analyses using gas chromatography mass spectrometry showed TCDF treatment altered the ratio of unsaturated/saturated fatty acids. Consistent with this observation, an increase in hepatic expression of stearoyl coenzyme A desaturase 1 was also observed. In addition, TCDF exposure resulted in inhibition of de novo fatty acid biosynthesis manifested by down-regulation of acetyl-CoA, malonyl-CoA and palmitoyl-CoA metabolites and related mRNA levels. In contrast, no significant changes in the levels of glucose and lipid were observed in serum and liver obtained from Ahr-null mice following TCDF treatment, thus strongly supporting the important role of the AHR in mediating the metabolic effects seen following TCDF exposure. PMID:26023891

  8. Combined therapeutic use of AdGFPFasL and small molecule inhibitors of ceramide metabolism in prostate and head and neck cancers: a status report.

    PubMed

    Norris, J S; Bielawska, A; Day, T; El-Zawahri, A; ElOjeimy, S; Hannun, Y; Holman, D; Hyer, M; Landon, C; Lowe, S; Dong, J Y; McKillop, J; Norris, K; Obeid, L; Rubinchik, S; Tavassoli, M; Tomlinson, S; Voelkel-Johnson, C; Liu, X

    2006-12-01

    As of January 2005, there were 1020 gene therapy clinical trials ongoing worldwide with 675 or 66.2% devoted to cancer gene therapy. The majority are occurring in the US and Europe (http://www.wiley.co.uk/genetherapy/clinical/). At the present time, to our knowledge there are no trials that employ gene delivery of Fas Ligand (FasL). As an important note, and in contrast to somatic cell therapy trials, there are no reported deaths due to therapeutic vector administration in any cancer gene therapy trial. That said, from our studies and from the published literature, the issue of gene delivery remains the major obstacle to successfully employing gene therapy for cancer treatment. Numerous laboratories are studying this with many different approaches. My co-workers and I have focused on the delivery issue by using various approaches that address tumor targeting and transgene expression. In addition, we are focusing on enhancing tumor cell killing via the bystander effect and through use of small molecules to enhance bystander activity. PMID:16763610

  9. Metabolic activity of sodium, measured by neutron activation, in the hands of patients suffering from bone diseases: concise communication

    SciTech Connect

    Spinks, T.J.; Bewley, D.K.; Paolillo, M.; Vlotides, J.; Joplin, G.F.; Ranicar, A.S.O.

    1980-01-01

    Turnover of sodium in the human hand was studied by neutron activation. Patients suffering from various metabolic abnormalities affecting the skeleton, who were undergoing routine neutron activation for the measurement of calcium, were investigated along with a group of healthy volunteers. Neutron activation labels the sodium atoms simultaneously and with equal probability regardless of the turnover time of individual body compartments. The loss of sodium can be described either by a sum of two exponentials or by a single power function. Distinctions between patients and normal subjects were not apparent from the exponential model but were brought out by the power function. The exponent of time in the latter is a measure of clearance rate. The mean values of this parameter in (a) a group of patients suffering from acromegaly; (b) a group including Paget's disease, osteoporosis, Cushing's disease, and hyperparathyroidism; and (c) a group of healthy subjects, were found to be significantly different from each other.

  10. Effects of sex and site on amino acid metabolism enzyme gene expression and activity in rat white adipose tissue

    PubMed Central

    Arriarán, Sofía; Agnelli, Silvia; Remesar, Xavier; Fernández-López, José Antonio

    2015-01-01

    Background and Objectives. White adipose tissue (WAT) shows marked sex- and diet-dependent differences. However, our metabolic knowledge of WAT, especially on amino acid metabolism, is considerably limited. In the present study, we compared the influence of sex on the amino acid metabolism profile of the four main WAT sites, focused on the paths related to ammonium handling and the urea cycle, as a way to estimate the extent of WAT implication on body amino-nitrogen metabolism. Experimental Design. Adult female and male rats were maintained, undisturbed, under standard conditions for one month. After killing them under isoflurane anesthesia. WAT sites were dissected and weighed. Subcutaneous, perigonadal, retroperitoneal and mesenteric WAT were analyzed for amino acid metabolism gene expression and enzyme activities. Results. There was a considerable stability of the urea cycle activities and expressions, irrespective of sex, and with only limited influence of site. Urea cycle was more resilient to change than other site-specialized metabolic pathways. The control of WAT urea cycle was probably related to the provision of arginine/citrulline, as deduced from the enzyme activity profiles. These data support a generalized role of WAT in overall amino-N handling. In contrast, sex markedly affected WAT ammonium-centered amino acid metabolism in a site-related way, with relatively higher emphasis in males’ subcutaneous WAT. Conclusions. We found that WAT has an active amino acid metabolism. Its gene expressions were lower than those of glucose-lipid interactions, but the differences were quantitatively less important than usually reported. The effects of sex on urea cycle enzymes expression and activity were limited, in contrast with the wider variations observed in other metabolic pathways. The results agree with a centralized control of urea cycle operation affecting the adipose organ as a whole. PMID:26587356

  11. Metabolic Potential and Activity in Fluids of the Coast Range Ophiolite Microbial Observatory, California, USA

    NASA Technical Reports Server (NTRS)

    Hoehler, T.; Som, S.; Schrenk, M.; McCollom, T.; Cardace, D.

    2016-01-01

    Metabolic potential and activity associated with hydrogen and carbon monoxide were characterized in fluids sampled from the the Coast Range Ophiolite Microbial Observatory (CROMO). CROMO consists of two clusters of science-dedicated wells drilled to varying depths up to 35m in the actively serpentinizing, Jurassic-age Coast Range Ophiolite of Northern California, along with a suite of pre-existing monitoring wells at the same site. Consistent with the fluid chemistry observed in other serpentinizing systems, CROMO fluids are highly alkaline, with pH up to 12.5, high in methane, with concentrations up 1600 micromolar, and low in dissolved inorganic carbon (DIC), with concentrations of 10's to 100's of micromolar. CROMO is conspicuous for fluid H2 concentrations that are consistently sub-micromolar, orders of magnitude lower than is typical of other systems. However, higher H2 concentrations (10's -100's of micromolar) at an earlier stage of fluid chemical evolution are predicted by, or consistent with: thermodynamic models for fluid chemistry based on parent rock composition equivalent to local peridotite and with water:rock ratio constrained by observed pH; the presence of magnetite at several wt% in CROMO drill cores; and concentrations of formate and carbon monoxide that would require elevated H2 if formed in equilibrium with H2 and DIC. Calculated Gibbs energy changes for reaction of H2 and CO in each of several metabolisms, across the range of fluid composition encompassed by the CROMO wells, range from bioenergetically feasible (capable of driving ATP synthesis) to thermodynamically unfavorable. Active consumption relative to killed controls was observed for both CO and H2 during incubation of fluids from the pre-existing monitoring wells; in incubations of freshly cored solids, consumption was only observed in one sample set (corresponding to the lowest pH) out of three. The specific metabolisms by which H2 and CO are consumed remain to be determined.

  12. Modeling and Classification of Kinetic Patterns of Dynamic Metabolic Biomarkers in Physical Activity.

    PubMed

    Breit, Marc; Netzer, Michael; Weinberger, Klaus M; Baumgartner, Christian

    2015-08-01

    The objectives of this work were the classification of dynamic metabolic biomarker candidates and the modeling and characterization of kinetic regulatory mechanisms in human metabolism with response to external perturbations by physical activity. Longitudinal metabolic concentration data of 47 individuals from 4 different groups were examined, obtained from a cycle ergometry cohort study. In total, 110 metabolites (within the classes of acylcarnitines, amino acids, and sugars) were measured through a targeted metabolomics approach, combining tandem mass spectrometry (MS/MS) with the concept of stable isotope dilution (SID) for metabolite quantitation. Biomarker candidates were selected by combined analysis of maximum fold changes (MFCs) in concentrations and P-values resulting from statistical hypothesis testing. Characteristic kinetic signatures were identified through a mathematical modeling approach utilizing polynomial fitting. Modeled kinetic signatures were analyzed for groups with similar behavior by applying hierarchical cluster analysis. Kinetic shape templates were characterized, defining different forms of basic kinetic response patterns, such as sustained, early, late, and other forms, that can be used for metabolite classification. Acetylcarnitine (C2), showing a late response pattern and having the highest values in MFC and statistical significance, was classified as late marker and ranked as strong predictor (MFC = 1.97, P < 0.001). In the class of amino acids, highest values were shown for alanine (MFC = 1.42, P < 0.001), classified as late marker and strong predictor. Glucose yields a delayed response pattern, similar to a hockey stick function, being classified as delayed marker and ranked as moderate predictor (MFC = 1.32, P < 0.001). These findings coincide with existing knowledge on central metabolic pathways affected in exercise physiology, such as β-oxidation of fatty acids, glycolysis, and glycogenolysis. The presented modeling approach

  13. Fast molecular evolution associated with high active metabolic rates in poison frogs.

    PubMed

    Santos, Juan C

    2012-08-01

    Molecular evolution is simultaneously paced by mutation rate, genetic drift, and natural selection. Life history traits also affect the speed of accumulation of nucleotide changes. For instance, small body size, rapid generation time, production of reactive oxygen species (ROS), and high resting metabolic rate (RMR) are suggested to be associated with faster rates of molecular evolution. However, phylogenetic correlation analyses failed to support a relationship between RMR and molecular evolution in ectotherms. In addition, RMR might underestimate the metabolic budget (e.g., digestion, reproduction, or escaping predation). An alternative is to test other metabolic rates, such as active metabolic rate (AMR), and their association with molecular evolution. Here, I present comparative analyses of the associations between life history traits (i.e., AMR, RMR, body mass, and fecundity) with rates of molecular evolution of and mitochondrial loci from a large ectotherm clade, the poison frogs (Dendrobatidae). My results support a strong positive association between mass-specific AMR and rates of molecular evolution for both mitochondrial and nuclear loci. In addition, I found weaker and genome-specific covariates such as body mass and fecundity for mitochondrial and nuclear loci, respectively. No direct association was found between mass-specific RMR and rates of molecular evolution. Thus, I provide a mechanistic hypothesis of the link between AMRs and the rate of molecular evolution based on an increase in ROS within germ line cells during periodic bouts of hypoxia/hyperoxia related to aerobic exercise. Finally, I propose a multifactorial model that includes AMR as a predictor of the rate of molecular evolution in ectothermic lineages.

  14. Modeling and Classification of Kinetic Patterns of Dynamic Metabolic Biomarkers in Physical Activity

    PubMed Central

    Breit, Marc; Netzer, Michael

    2015-01-01

    The objectives of this work were the classification of dynamic metabolic biomarker candidates and the modeling and characterization of kinetic regulatory mechanisms in human metabolism with response to external perturbations by physical activity. Longitudinal metabolic concentration data of 47 individuals from 4 different groups were examined, obtained from a cycle ergometry cohort study. In total, 110 metabolites (within the classes of acylcarnitines, amino acids, and sugars) were measured through a targeted metabolomics approach, combining tandem mass spectrometry (MS/MS) with the concept of stable isotope dilution (SID) for metabolite quantitation. Biomarker candidates were selected by combined analysis of maximum fold changes (MFCs) in concentrations and P-values resulting from statistical hypothesis testing. Characteristic kinetic signatures were identified through a mathematical modeling approach utilizing polynomial fitting. Modeled kinetic signatures were analyzed for groups with similar behavior by applying hierarchical cluster analysis. Kinetic shape templates were characterized, defining different forms of basic kinetic response patterns, such as sustained, early, late, and other forms, that can be used for metabolite classification. Acetylcarnitine (C2), showing a late response pattern and having the highest values in MFC and statistical significance, was classified as late marker and ranked as strong predictor (MFC = 1.97, P < 0.001). In the class of amino acids, highest values were shown for alanine (MFC = 1.42, P < 0.001), classified as late marker and strong predictor. Glucose yields a delayed response pattern, similar to a hockey stick function, being classified as delayed marker and ranked as moderate predictor (MFC = 1.32, P < 0.001). These findings coincide with existing knowledge on central metabolic pathways affected in exercise physiology, such as β-oxidation of fatty acids, glycolysis, and glycogenolysis. The presented modeling approach

  15. Prokaryotic diversity and metabolically active microbial populations in sediments from an active mud volcano in the Gulf of Mexico.

    PubMed

    Martinez, Robert J; Mills, Heath J; Story, Sandra; Sobecky, Patricia A

    2006-10-01

    In this study, ribosomes and genomic DNA were extracted from three sediment depths (0-2, 6-8 and 10-12 cm) to determine the vertical changes in the microbial community composition and identify metabolically active microbial populations in sediments obtained from an active seafloor mud volcano site in the northern Gulf of Mexico. Domain-specific Bacteria and Archaea 16S polymerase chain reaction primers were used to amplify 16S rDNA gene sequences from extracted DNA. Complementary 16S ribosomal DNA (crDNA) was obtained from rRNA extracted from each sediment depth that had been subjected to reverse transcription polymerase chain reaction amplification. Twelve different 16S clone libraries, representing the three sediment depths, were constructed and a total of 154 rDNA (DNA-derived) and 142 crDNA (RNA-derived) Bacteria clones and 134 rDNA and 146 crDNA Archaea clones obtained. Analyses of the 576 clones revealed distinct differences in the composition and patterns of metabolically active microbial phylotypes relative to sediment depth. For example, epsilon-Proteobacteria rDNA clones dominated the 0-2 cm clone library whereas gamma-Proteobacteria dominated the 0-2 cm crDNA library suggesting gamma to be among the most active in situ populations detected at 0-2 cm. Some microbial lineages, although detected at a frequency as high as 9% or greater in the total DNA library (i.e. Actinobacteria, alpha-Proteobacteria), were markedly absent from the RNA-derived libraries suggesting a lack of in situ activity at any depth in the mud volcano sediments. This study is one of the first to report the composition of the microbial assemblages and physiologically active members of archaeal and bacterial populations extant in a Gulf of Mexico submarine mud volcano. PMID:16958759

  16. Reduction in hepatic drug metabolizing CYP3A4 activities caused by P450 oxidoreductase mutations identified in patients with disordered steroid metabolism

    SciTech Connect

    Flueck, Christa E.; Mullis, Primus E.; Pandey, Amit V.

    2010-10-08

    Research highlights: {yields} Cytochrome P450 3A4 (CYP3A4), metabolizes 50% of drugs in clinical use and requires NADPH-P450 reductase (POR). {yields} Mutations in human POR cause congenital adrenal hyperplasia from diminished activities of steroid metabolizing P450s. {yields} We are reporting that mutations in POR may reduce CYP3A4 activity. {yields} POR mutants Y181D, A457H, Y459H, V492E and R616X lost 99%, while A287P, C569Y and V608F lost 60-85% CYP3A4 activity. {yields} Reduction of CYP3A4 activity may cause increased risk of drug toxicities/adverse drug reactions in patients with POR mutations. -- Abstract: Cytochrome P450 3A4 (CYP3A4), the major P450 present in human liver metabolizes approximately half the drugs in clinical use and requires electrons supplied from NADPH through NADPH-P450 reductase (POR, CPR). Mutations in human POR cause a rare form of congenital adrenal hyperplasia from diminished activities of steroid metabolizing P450s. In this study we examined the effect of mutations in POR on CYP3A4 activity. We used purified preparations of wild type and mutant human POR and in vitro reconstitution with purified CYP3A4 to perform kinetic studies. We are reporting that mutations in POR identified in patients with disordered steroidogenesis/Antley-Bixler syndrome (ABS) may reduce CYP3A4 activity, potentially affecting drug metabolism in individuals carrying mutant POR alleles. POR mutants Y181D, A457H, Y459H, V492E and R616X had more than 99% loss of CYP3A4 activity, while POR mutations A287P, C569Y and V608F lost 60-85% activity. Loss of CYP3A4 activity may result in increased risk of drug toxicities and adverse drug reactions in patients with POR mutations.

  17. Role of AMP-activated protein kinase in metabolic depression in animals.

    PubMed

    Rider, Mark H

    2016-01-01

    AMP-activated protein kinase (AMPK) is a highly conserved eukaryotic protein serine/threonine kinase that controls cellular and whole body energy homoeostasis. AMPK is activated during energy stress by a rise in AMP:ATP ratio and maintains energy balance by phosphorylating targets to switch on catabolic ATP-generating pathways, while at the same time switching off anabolic ATP-consuming processes. Metabolic depression is a strategy used by many animals to survive environmental stress and has been extensively studied across phylogeny by comparative biochemists and physiologists, but the role of AMPK has only recently been addressed. This review first deals with the evolution of AMPK in eukaryotes (excluding plants and fungi) and its regulation. Changes in adenine nucleotides and AMPK activation are described in animals during environmental energy stress, before considering the involvement of AMPK in controlling β-oxidation, fatty acid synthesis, triacylglycerol mobilization and protein synthesis. Lastly, strategies are presented to validate the role of AMPK in mediating metabolic depression by phosphorylating downstream targets.

  18. Metabolic stress–induced activation of FoxO1 triggers diabetic cardiomyopathy in mice

    PubMed Central

    Battiprolu, Pavan K.; Hojayev, Berdymammet; Jiang, Nan; Wang, Zhao V.; Luo, Xiang; Iglewski, Myriam; Shelton, John M.; Gerard, Robert D.; Rothermel, Beverly A.; Gillette, Thomas G.; Lavandero, Sergio; Hill, Joseph A.

    2012-01-01

    The leading cause of death in diabetic patients is cardiovascular disease; diabetic cardiomyopathy is typified by alterations in cardiac morphology and function, independent of hypertension or coronary disease. However, the molecular mechanism that links diabetes to cardiomyopathy is incompletely understood. Insulin resistance is a hallmark feature of diabetes, and the FoxO family of transcription factors, which regulate cell size, viability, and metabolism, are established targets of insulin and growth factor signaling. Here, we set out to evaluate a possible role of FoxO proteins in diabetic cardiomyopathy. We found that FoxO proteins were persistently activated in cardiac tissue in mice with diabetes induced either genetically or by high-fat diet (HFD). FoxO activity was critically linked with development of cardiomyopathy: cardiomyocyte-specific deletion of FoxO1 rescued HFD-induced declines in cardiac function and preserved cardiomyocyte insulin responsiveness. FoxO1-depleted cells displayed a shift in their metabolic substrate usage, from free fatty acids to glucose, associated with decreased accumulation of lipids in the heart. Furthermore, we found that FoxO1-dependent downregulation of IRS1 resulted in blunted Akt signaling and insulin resistance. Together, these data suggest that activation of FoxO1 is an important mediator of diabetic cardiomyopathy and is a promising therapeutic target for the disease. PMID:22326951

  19. [Cytokines profile and metabolic activity of neutrophils of peripheral blood when progressing neoplasma].

    PubMed

    Abakumova, T V; Antoneeva, I I; Gening, T P; Gening, S O; Dolgova, D R; Fomina, A V

    2014-01-01

    The neutrophil is considered as the peculiar monocelled sekretorny gland realizing the effector potential including by secretion of soluble products - cytokines and for today. Influence of a tumor on functional activity of neutrophils depends on type, localization and a stage of its development. In our research dynamics of metabolic and of neutrophils of peripheral blood, the contents in a lysate and serums of blood of cytokines of IL-1β, 1Ra, 2, 6, 10, 18, TNF-α, IFN-γ and is studied when progressing a cervical cancer. Cytokines and metabolism indicators - activity of, determined by an immunofermental method, level of cationic proteins, a share of active cages in the spontaneous NST-test were cytochemical. It is shown that when progressing cervical cancer against increase in total of neutrophils significant decrease in their, aerobic and anaerobic bacterial action, decrease in the IL-1β and IL-1 Ra level, and also IFN-γ takes place at TNF-α increase, increase of production of matrix metalloproteinas-2 on Ib-IIa of a stage of a disease that allows to assume emergence at this stage of cervical cancer of pro-tumoral effect of neutrophils.

  20. Biophysical model for integrating neuronal activity, EEG, fMRI and metabolism.

    PubMed

    Sotero, Roberto C; Trujillo-Barreto, Nelson J

    2008-01-01

    Our goal is to model the coupling between neuronal activity, cerebral metabolic rates of glucose and oxygen consumption, cerebral blood flow (CBF), electroencephalography (EEG) and blood oxygenation level-dependent (BOLD) responses. In order to accomplish this, two previous models are coupled: a metabolic/hemodynamic model (MHM) for a voxel, linking BOLD signals and neuronal activity, and a neural mass model describing the neuronal dynamics within a voxel and its interactions with voxels of the same area (short-range interactions) and other areas (long-range interactions). For coupling both models, we take as the input to the BOLD model, the number of active synapses within the voxel, that is, the average number of synapses that will receive an action potential within the time unit. This is obtained by considering the action potentials transmitted between neuronal populations within the voxel, as well as those arriving from other voxels. Simulations are carried out for testing the integrated model. Results show that realistic evoked potentials (EP) at electrodes on the scalp surface and the corresponding BOLD signals for each voxel are produced by the model. In another simulation, the alpha rhythm was reproduced and reasonable similarities with experimental data were obtained when calculating correlations between BOLD signals and the alpha power curve. The origin of negative BOLD responses and the characteristics of EEG, PET and BOLD signals in Alzheimer's disease were also studied. PMID:17919931

  1. The Emerging Nexus of Active DNA Demethylation and Mitochondrial Oxidative Metabolism in Post-Mitotic Neurons

    PubMed Central

    Meng, Huan; Chen, Guiquan; Gao, Hui-Ming; Song, Xiaoyu; Shi, Yun; Cao, Liu

    2014-01-01

    The variable patterns of DNA methylation in mammals have been linked to a number of physiological processes, including normal embryonic development and disease pathogenesis. Active removal of DNA methylation, which potentially regulates neuronal gene expression both globally and gene specifically, has been recently implicated in neuronal plasticity, learning and memory processes. Model pathways of active DNA demethylation involve ten-eleven translocation (TET) methylcytosine dioxygenases that are dependent on oxidative metabolites. In addition, reactive oxygen species (ROS) and oxidizing agents generate oxidative modifications of DNA bases that can be removed by base excision repair proteins. These potentially link the two processes of active DNA demethylation and mitochondrial oxidative metabolism in post-mitotic neurons. We review the current biochemical understanding of the DNA demethylation process and discuss its potential interaction with oxidative metabolism. We then summarise the emerging roles of both processes and their interaction in neural plasticity and memory formation and the pathophysiology of neurodegeneration. Finally, possible therapeutic approaches for neurodegenerative diseases are proposed, including reprogramming therapy by global DNA demethylation and mitohormesis therapy for locus-specific DNA demethylation in post-mitotic neurons. PMID:25490140

  2. Genotoxicity induced by a shale oil byproduct in Chinese hamster cells following metabolic activation

    SciTech Connect

    Okinaka, R.T.; Nickols, J.W.; Chen, D.J.; Strniste, G.F.

    1982-01-01

    A process water obtained from a holding tank during the surface retorting of oil shale has been shown to induce a linear dose response of 100 histidine revertants/sub ..mu../1 in the Ames/Salmonella test. The complex mixture has also previously been shown to induce genotoxicity in mammalian cells following activation by near ultraviolet light and natural sunlight. This report focuses on the effects of a particular oil shale retort process water on cultured Chinese hamster cells following metabolic activation by either rat liver homogenate or lethally irradiated but metabolically competent Syrian hamster embryonic cells. Cytotoxic and mutagenic responses induced by the process water and a fractionated sample from it containing the majority of the mutagenic activity (as assessed by the Salmonella test) were measured under conditions designed to optimally measure the mutagenic potency of the promutagen, benzo(a)pyrene. These results suggest a possible discrepancy in the genotoxic potential of this complex mixture when various methods are utilized to measure its potential.

  3. US space flight experience. Physical exertion and metabolic demand of extravehicular activity: Past, present, and future

    NASA Technical Reports Server (NTRS)

    Moore, Thomas P.

    1989-01-01

    A review of physical exertion and metabolic demands of extravehicular activity (EVA) on U.S. astronauts is given. Information is given on EVA during Gemini, Apollo and Skylab missions. It is noted that nominal EVA's should not be overstressful from a cardiovascular standpoint; that manual-intensive EVA's such as are planned for the construction phase of the Space Station can and will be demanding from a muscular standpoint, primarily for the upper extremities; that off-nominal unplanned EVA's can be physically demanding both from an endurance and from a muscular standpoint; and that crewmembers should be physically prepared and capable of performing these EVA's at any time during the mission.

  4. Metabolism of radio-labelled C3: effects of in vivo activation in rabbits

    PubMed Central

    Charlesworth, J. A.; Williams, D. G.; Naish, P.; Lachmann, P. J.; Peters, D. K.

    1974-01-01

    Turnover studies were performed in rabbits using biologically screened, highly purified, radio-labelled human C3 and C3c. Experiments were also carried out using agents known to activate the complement system in vivo—cobra venom factor, human nephritic serum and nephrotoxic antibody to rabbit glomerular basement membrane. Activation of labelled C3 by cobra factor provided information regarding the metabolic behaviour of C3d. The fractional catabolic ratio (FCR) of human C3 in normal rabbits was 2·4–2·8% of the plasma pool per hr. FCR for C3c was 4.5% per hr. Activation of C3 in vivo consistently resulted in accelerated disappearance of plasma radioactivity. Analysis of the plasma and total body radioactivity curves indicated that both hypercatabolism and extravascular sequestration of radioactivity were responsible for this phenomenon. PMID:4468849

  5. Evidence of active tectonics on a Roman aqueduct system (II-III century A.D.) near Rome, Italy

    NASA Astrophysics Data System (ADS)

    Marra, Fabrizio; Montone, Paola; Pirro, Mario; Boschi, Enzo

    2004-04-01

    In this paper we describe evidence of strong tectonic deformation affecting two aqueducts of Roman age (II-III century A.D.). The channels are located approximately 20 km northeast of Rome along the ancient Via Tiburtina. Brittle and ductile deformation affects these two structures, including extensional joint systems, NE-oriented faults, and horizontal distortion. This deformation is consistent with right-lateral movement on major N-striking faults, and represents the first evidence that tectonic deformation took place in historical times in the vicinity of Rome, with local strike-slip movement superimposed on a regional extensional fault system.

  6. Aerobic and anaerobic metabolism in smooth muscle cells of taenia coli in relation to active ion transport.

    PubMed

    Casteels, R; Wuytack, F

    1975-09-01

    1. The O2 consumption and lactic acid production of the guinea-pig's taenia coli have been studied in relation to the active Na-K transport, in order to estimate the ratio: active Na extrusion/active K uptake/ATP hydrolysis. 2. By applying different procedures of partial metabolic ingibition, it was found that a reactivation of the active Na-K transport in K-depleted tissues could occur in an anaerobic medium, provided glucose was present and in an aerobic medium free of added metabolizable substrate. The active Na-K transport was rapidly blocked in an anaerobic-substrate free medium. 3. Readmission of K to K-depleted tissues under aerobic conditions stimulates both O2 consumption and lactic acid production. While the O2 consumption creeps up slowly and requires 50 min to reach control values, the aerobic lactic acid production increases to a maximum within 10 min and decreases again during the next 50 min to its steady-state value. 4. A reactivation of the Na-pump in K-depleted cells in a N2-glucose medium causes an immediate increase of the lactic acid production, which decreases to its control value after 60 min. The maximal increase in anaerobic lactic acid production during reactivation of the Na-K pump is a function of [K]O. The system can be cescribed with first order kinetics having a Vmax = 0-72 mumole.g-1 f. wt. min-1 and a Km = 1-1 mM. 5. By varying the glucose concentration of [K]O during reactivation of the Na-K pump, different Na-K pumping rates can be obtained. The ratios net Na extrusion/ATP or net K accumulation/ATP amount to -1-32 +/- 0-19 (36) and 1-02 +/- 0-11 (36), in the experiments with different glucose concentrations. Taking into account the interference by net passive fluxes, one can estimate a ratio:active Na transport/active K transport/ATP, of 1-7/0-8/1. This ratio is not very different from the values observed in other tissues.

  7. Postprandial activation of metabolic and inflammatory signalling pathways in human peripheral mononuclear cells.

    PubMed

    Ehlers, Kerstin; Brand, Tina; Bangert, Adina; Hauner, Hans; Laumen, Helmut

    2014-06-28

    High-fat, high-carbohydrate (HFHC) meals induce an inflammatory response in mononuclear cells (MNC). Here, we studied the interaction between metabolic and inflammatory signalling pathways by the measurement of postprandial effects of three different test meals on intracellular Akt, S6 kinase (S6K)/mammalian target of rapamycin and NF-κB signalling in human MNC. We recruited six healthy, lean individuals. Each individual ingested three different meals in the morning separated by at least 3 d: a HFHC meal; an oral lipid-tolerance test meal; a healthy breakfast. Blood samples were obtained before and 1, 2, 4, 6 and 8 h after ingestion. Plasma insulin and IL-6 levels were measured. Intracellular metabolic and inflammatory signalling pathways were assessed by measuring the phosphorylation of Akt kinase and S6K, the degradation of inhibitory κB-α (IκB-α) protein and the DNA binding activity of NF-κB in MNC. mRNA expression levels of the Akt and NF-κB target genes Mn superoxide dismutase (MnSOD), CC-chemokine-receptor 5 (CCR5), intercellular adhesion molecule 1 (ICAM-1) and plasminogen activator inhibitor-1 (PAI-1) were measured by quantitative RT-PCR. We found a positive correlation of Akt phosphorylation with NF-κB activation (NF-κB binding activity: r 0·4500, P= 0·0003; IκB-α protein levels: r -0·5435, P< 0·0001), a negative correlation of plasma insulin levels with NF-κB binding activity (r -0·3993, P= 0·0016) and a positive correlation of plasma insulin levels with S6K activation (r 0·4786, P< 0·0001). The activation of Akt and pro-inflammatory NF-κB signalling was supported by the up-regulation of the respective target genes MnSOD and CCR5. In conclusion, the present data suggest a postprandial interaction between the metabolic and inflammatory signalling pathways Akt and NF-κB in MNC.

  8. Hydroperoxide Lyase and Other Hydroperoxide-Metabolizing Activity in Tissues of Soybean, Glycine max

    PubMed Central

    Gardner, Harold W.; Weisleder, David; Plattner, Ronald D.

    1991-01-01

    Hydroperoxide lyase (HPLS) activity in soybean (Glycine max) seed/seedlings, leaves, and chloroplasts of leaves required detergent solubilization for maximum in vitro activity. On a per milligram of protein basis, more HPLS activity was found in leaves, especially chloroplasts, than in seeds or seedlings. The total yield of hexanal from 13(S)-hydroperoxy-cis-9,trans-11-octadecadienoic acid (13S-HPOD) from leaf or chloroplast preparations was 58 and 66 to 85%, respectively. Because of significant competing hydroperoxide-metabolizing activities from other enzymes in seed/seedling preparations, the hexanal yields from this source were lower (36-56%). Some of the products identified from the seed or seedling preparations indicated that the competing activity was mainly due to both a hydroperoxide peroxygenase and reactions catalyzed by lipoxygenase. Different HPLS isozyme compositions in the seed/seedling versus the leaf/chloroplast preparations were indicated by differences in the activity as a function of pH, the Km values, relative Vmax with 13S-HPOD and 13(S)-hydroperoxy-cis-9,trans-11,cis-15-octadecatrienoic acid (13S-HPOT), and the specificity with different substrates. With regard to the latter, both seed/seedling and chloroplast HPLS utilized the 13S-HPOD and 13S-HPOT substrates, but only seeds/seedlings were capable of metabolizing 9(S)-hydroperoxy-trans-10,cis-12-octadecadienoic acid into 9-oxononanoic acid, isomeric nonenals, and 4-hydroxynonenal. From 13S-HPOD and 13S-HPOT, the products were identified as 12-oxo-cis-9-dodecenoic acid, as well as hexanal from 13S-HPOD and cis-3-hexenal from 13S-HPOT. In seed preparations, there was partial isomerization of the cis-3 or cis-9 into trans-2 or trans-10 double bonds, respectively. PMID:16668490

  9. In Vitro Bactericidal and Associated Metabolic Activities of Mouse Spleen Cells 1

    PubMed Central

    Strauss, R. R.; Paul, B. B.; Jacobs, A. A.; Sbarra, A. J.

    1972-01-01

    Spleen cell suspensions from AKR and CD-1 mice are able to kill Escherichia coli in vitro. The optimal ratio of splenocytes to bacteria for this activity is 1: 1. Incubation of these cells with inert polystyrene latex spherules (0.81 μm diameter) results in a fourfold increase in glucose-1-14C oxidation. Under these conditions, there is also a 2.5-fold increase in both reduced nicotinamide adenine dinucleotide phosphate oxidase activity and formate oxidation. Spleen cell fractions have been shown to have significant peroxidase activity. This has been quantitated by the guaiacol oxidation method. The 20,000 × g pellet fraction of spleen cell homogenate can kill E. coli when H2O2 and chloride ions are added and the reaction is carried out at pH 5.5 and 37 C. PMID:4144202

  10. Metabolic evidence that serosal sodium does not recycle through the active transepithelial transport pathway of toad bladder.

    PubMed

    Canessa, M; Labarca, P; Leaf, A

    1976-12-25

    The possibility that sodium from the serosal bathing medium "back diffuses" into the active sodium transport pool within the mucosal epithelial cell of the isolated toad bladder was examined by determining the effect on the metabolism of the tissue of removing sodium from the serosal medium. It was expected that if recycling of serosal sodium did occur through the active transepithelial transport pathway of the isolated toad bladder, removal of sodium from the serosal medium would reduce the rate of CO2 production by the tissue and enhance of stoichiometric ratio of sodium ions transported across the bladder per molecula of sodium transport dependent CO2 produced simultaneously by the bladder (JNa/JCO2). The data revealed no significant change in this ratio (17.19 with serosal sodium and 16.13 after replacing serosal sodium with choline). Further, when transepithelial sodium transport was inhibited (a) by adding amiloride to the mucosal medium, or (b) by removing sodium from the mucosal medium, subsequent removal of sodium from the serosal medium, or (c) addition of ouabain failed to depress the basal rate of CO2 production by the bladder [(a)rate of basal, nontransport related, CO2 production (JbCO2) equals 1.54 +/- 0.52 with serosal sodium and 1.54 +/- 0.37 without serosal sodium; (b) Jb CO2 equals 2.18 +/- 0.21 with serosal sodium and 2.09 +/- 0.21 without serosal sodium; (c) 1.14 +/- 0.26 without ouabain and 1.13 +/- 0.25 with ouabain; unite of JbCO2 are nmoles mg d.w.-1 min-1]. The results support the hypothesis that little, if any, recycling of serosal sodium occurs in the total bladder.

  11. Liver X Receptors Regulate the Transcriptional Activity of the Glucocorticoid Receptor: Implications for the Carbohydrate Metabolism

    PubMed Central

    Nader, Nancy; Ng, Sinnie Sin Man; Wang, Yonghong; Abel, Brent S.; Chrousos, George P.; Kino, Tomoshige

    2012-01-01

    GLUCOCORTICOIDS are steroid hormones that strongly influence intermediary carbohydrate metabolism by increasing the transcription rate of glucose-6-phosphatase (G6Pase), a key enzyme of gluconeogenesis, and suppress the immune system through the glucocorticoid receptor (GR). The liver X receptors (LXRs), on the other hand, bind to cholesterol metabolites, heterodimerize with the retinoid X receptor (RXR), and regulate the cholesterol turnover, the hepatic glucose metabolism by decreasing the expression of G6Pase, and repress a set of inflammatory genes in immune cells. Since the actions of these receptors overlap with each other, we evaluated the crosstalk between the GR- and LXR-mediated signaling systems. Transient transfection-based reporter assays and gene silencing methods using siRNAs for LXRs showed that overexpression/ligand (GW3965) activation of LXRs/RXRs repressed GR-stimulated transactivation of certain glucocorticoid response element (GRE)-driven promoters in a gene-specific fashion. Activation of LXRs by GW3965 attenuated dexamethasone-stimulated elevation of circulating glucose in rats. It also suppressed dexamethasone-induced mRNA expression of hepatic glucose-6-phosphatase (G6Pase) in rats, mice and human hepatoma HepG2 cells, whereas endogenous, unliganded LXRs were required for dexamethasone-induced mRNA expression of phosphoenolpyruvate carboxylase. In microarray transcriptomic analysis of rat liver, GW3965 differentially regulated glucocorticoid-induced transcriptional activity of about 15% of endogenous glucocorticoid-responsive genes. To examine the mechanism through which activated LXRs attenuated GR transcriptional activity, we examined LXRα/RXRα binding to GREs. Endogenous LXRα/RXRα bound GREs and inhibited GR binding to these DNA sequences both in in vitro and in vivo chromatin immunoprecipitation assays, while their recombinant proteins did so on classic or G6Pase GREs in gel mobility shift assays. We propose that administration of

  12. Probing Metabolic Activity of Deep Subseafloor Life with NanoSIMS

    NASA Astrophysics Data System (ADS)

    Morono, Y.; Terada, T.; Itoh, M.; Inagaki, F.

    2014-12-01

    There are very few natural environments where life is absent in the Earth's surface biosphere. However, uninhabitable region is expected to be exist in the deep subsurface biosphere, of which extent and constraining factor(s) have still remained largly unknown. Scientific ocean drilling have revealed that microbial communities in sediments are generally phylogenetically distinct from known spieces isolated from the Earth's surface biosphere, and hence metabolic functions of the deep subseafloor life remain unknown. In addition, activity of subseafloor microbial cells are thought to be extraordinally slow, as indicated by limited supply of neutrient and energy substrates. To understand the limits of the Earth's subseafloor biosphere and metabolic functions of microbial populations, detection and quantification of the deeply buried microbial cells in geological habitats are fundamentary important. Using newly developed cell separation techniques as well as an discriminative cell detection system, the current quantification limit of sedimentary microbial cells approaches to 102 cells/cm3. These techniques allow not only to assess very small microbial population close to the subsurface biotic fringe, but also to separate and sort the target cells using flow cytometric cell sorter. Once the deep subseafloor microbial cells are detached from mineral grains and sorted, it opens new windows to subsequent molecular ecological and element/isotopic analyses. With a combined use of nano-scale secondary ion masspectrometry (NanoSIMS) and stable isotope-probing techniques, it is possible to detect and measure activity of substrate incorporation into biomass, even for extremely slow metabolic processes such as uncharacteriszed deep subseafloor life. For example, it was evidenced by NanoSIMS that at least over 80% of microbial cells at ~200 meters-deep, 460,000-year-old sedimentary habitat are indeed live, which substrate incooporation was found to be low (10-15 gC/cell/day) even

  13. Field studies on the annual activity and the metabolic responses of a land snail population living in high altitude.

    PubMed

    Staikou, Alexandra; Tachtatzis, George; Feidantsis, Konstantinos; Michaelidis, Basile

    2016-01-01

    In the context of the metabolic cold adaptation hypothesis (MCA), we investigated a) the life and activity cycle characteristics and b) the metabolic responses of the endemic land snail species Cattania trizona olympica living at 1100m altitude in Olympus mountain (Greece). Field observations on the annual activity cycle of C. trizona olympica revealed that snails' activity was restricted mainly between the end of May and September, when the higher temperatures were recorded, while first matings were recorded in July and the last ones in mid September indicating a restricted favorable time period for reproduction. The activities of enzymes of intermediate metabolism showed a periodic seasonal pattern of change which seems to be closely related to the pattern of annual changes of air temperature and most of them exhibited higher activities during the coldest and warmest periods of the year. Moreover the data indicate a distinct differentiation of fuel oxidation during arousal and reproductive periods with lipid oxidation, apart from carbohydrates, contributing significantly to ATP turnover during reproductive activity. The higher enzymatic activities, determined in the tissues of C. trizona olympica than the corresponding ones determined in the tissues of the land snail species living at low altitudes, might indicate higher sensitivity of the intermediate metabolism and ATP turnover in C. trizona olympica to changes in environmental factors. Although the latter seems to be in line with the MCA hypothesis, it needs further investigation on metabolic rates to support it. PMID:26408810

  14. Hormonal and metabolic regulation of tomato fruit sink activity and yield under salinity

    PubMed Central

    Albacete, Alfonso; Cantero-Navarro, Elena; Balibrea, María E.; Großkinsky, Dominik K.; de la Cruz González, María; Martínez-Andújar, Cristina; Smigocki, Ann C.; Roitsch, Thomas; Pérez-Alfocea, Francisco

    2014-01-01

    Salinization of water and soil has a negative impact on tomato (Solanum lycopersicum L.) productivity by reducing growth of sink organs and by inducing senescence in source leaves. It has been hypothesized that yield stability implies the maintenance or increase of sink activity in the reproductive structures, thus contributing to the transport of assimilates from the source leaves through changes in sucrolytic enzymes and their regulation by phytohormones. In this study, classical and functional physiological approaches have been integrated to study the influence of metabolic and hormonal factors on tomato fruit sink activity, growth, and yield: (i) exogenous hormones were applied to plants, and (ii) transgenic plants overexpressing the cell wall invertase (cwInv) gene CIN1 in the fruits and de novo cytokinin (CK) biosynthesis gene IPT in the roots were constructed. Although salinity reduces fruit growth, sink activity, and trans-zeatin (tZ) concentrations, it increases the ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC) during the actively growing period (25 days after anthesis). Indeed, exogenous application of the CK analogue kinetin to salinized actively growing fruits recovered sucrolytic activities (mainly cwInv and sucrose synthase), sink strength, and fruit weight, whereas the ethylene-releasing compound ethephon had a negative effect in equivalent non-stressed fruits. Fruit yield was increased by both the constitutive expression of CIN1 in the fruits (up to 4-fold) or IPT in the root (up to 30%), owing to an increase in the fruit number (lower flower abortion) and in fruit weight. This is possibly related to a recovery of sink activity in reproductive tissues due to both (i) increase in sucrolytic activities (cwInv, sucrose synthase, and vacuolar and cytoplasmic invertases) and tZ concentration, and (ii) a decrease in the ACC levels and the activity of the invertase inhibitor. This study provides new functional evidences about the role of

  15. Hormonal and metabolic regulation of tomato fruit sink activity and yield under salinity.

    PubMed

    Albacete, Alfonso; Cantero-Navarro, Elena; Balibrea, María E; Großkinsky, Dominik K; de la Cruz González, María; Martínez-Andújar, Cristina; Smigocki, Ann C; Roitsch, Thomas; Pérez-Alfocea, Francisco

    2014-11-01

    Salinization of water and soil has a negative impact on tomato (Solanum lycopersicum L.) productivity by reducing growth of sink organs and by inducing senescence in source leaves. It has been hypothesized that yield stability implies the maintenance or increase of sink activity in the reproductive structures, thus contributing to the transport of assimilates from the source leaves through changes in sucrolytic enzymes and their regulation by phytohormones. In this study, classical and functional physiological approaches have been integrated to study the influence of metabolic and hormonal factors on tomato fruit sink activity, growth, and yield: (i) exogenous hormones were applied to plants, and (ii) transgenic plants overexpressing the cell wall invertase (cwInv) gene CIN1 in the fruits and de novo cytokinin (CK) biosynthesis gene IPT in the roots were constructed. Although salinity reduces fruit growth, sink activity, and trans-zeatin (tZ) concentrations, it increases the ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC) during the actively growing period (25 days after anthesis). Indeed, exogenous application of the CK analogue kinetin to salinized actively growing fruits recovered sucrolytic activities (mainly cwInv and sucrose synthase), sink strength, and fruit weight, whereas the ethylene-releasing compound ethephon had a negative effect in equivalent non-stressed fruits. Fruit yield was increased by both the constitutive expression of CIN1 in the fruits (up to 4-fold) or IPT in the root (up to 30%), owing to an increase in the fruit number (lower flower abortion) and in fruit weight. This is possibly related to a recovery of sink activity in reproductive tissues due to both (i) increase in sucrolytic activities (cwInv, sucrose synthase, and vacuolar and cytoplasmic invertases) and tZ concentration, and (ii) a decrease in the ACC levels and the activity of the invertase inhibitor. This study provides new functional evidences about the role of

  16. Activity of xenobiotic-metabolizing enzymes in the liver of rats with multi-vitamin deficiency.

    PubMed

    Tutelyan, Victor A; Kravchenko, Lidia V; Aksenov, Ilya V; Trusov, Nikita V; Guseva, Galina V; Kodentsova, Vera M; Vrzhesinskaya, Oksana A; Beketova, Nina A

    2013-01-01

    The purpose of the study was to determine how multi-vitamin deficiency affects xenobiotic-metabolizing enzyme (XME) activities in the rat liver. Vitamin levels and XME activities were studied in the livers of male Wistar rats who were fed for 4 weeks with semi-synthetic diets containing either adequate (100 % of recommended vitamin intake) levels of vitamins (control), or decreased vitamin levels (50 % or 20 % of recommended vitamin intake). The study results have shown that moderate vitamin deficiency (50 %) leads to a decrease of vitamin A levels only, and to a slight increase, as compared with the control, in the following enzyme activities: methoxyresorufin O-dealkylase (MROD) activity of CYP1 A2 - by 34 % (p < 0.05), UDP-glucuronosyl transferase - by 26 % (p < 0.05), and quinone reductase - by 55 % (p < 0.05). Profound vitamin deficiency (20 %) led to a decrease of vitamins A, E, B1, B2, and C, and enzyme activities in the liver: MROD - to 78 % of the control level (p < 0.05), 4-nitrophenol hydroxylase - to 74 % (p < 0.05), heme oxygenase-1 - to 83 % (p < 0.05), and quinone reductase - to 60 % (p < 0.05). At the same time, the UDP-glucuronosyl transferase activity and ethoxyresorufin O-dealkylase activity of CYP1A1, pentoxyresorufin O-dealkylase activity of CYP2B1/2 and 6β-testosterone hydroxylase, as well as the total activity of glutathione transferase did not differ from the control levels. The study has demonstrated that profound multi-vitamin deficiency is associated with a decrease in the expression of CYP1A2 and CYP3A1 mRNAs to 62 % and 79 %, respectively. These data indicated that a short-term but profound multi-vitamin deficiency in rats leads to a decrease in the activities and expression of the some XME that play an important role in detoxification of xenobiotics and metabolism of drugs and antioxidant protection. PMID:24220160

  17. Hormonal and metabolic regulation of tomato fruit sink activity and yield under salinity.

    PubMed

    Albacete, Alfonso; Cantero-Navarro, Elena; Balibrea, María E; Großkinsky, Dominik K; de la Cruz González, María; Martínez-Andújar, Cristina; Smigocki, Ann C; Roitsch, Thomas; Pérez-Alfocea, Francisco

    2014-11-01

    Salinization of water and soil has a negative impact on tomato (Solanum lycopersicum L.) productivity by reducing growth of sink organs and by inducing senescence in source leaves. It has been hypothesized that yield stability implies the maintenance or increase of sink activity in the reproductive structures, thus contributing to the transport of assimilates from the source leaves through changes in sucrolytic enzymes and their regulation by phytohormones. In this study, classical and functional physiological approaches have been integrated to study the influence of metabolic and hormonal factors on tomato fruit sink activity, growth, and yield: (i) exogenous hormones were applied to plants, and (ii) transgenic plants overexpressing the cell wall invertase (cwInv) gene CIN1 in the fruits and de novo cytokinin (CK) biosynthesis gene IPT in the roots were constructed. Although salinity reduces fruit growth, sink activity, and trans-zeatin (tZ) concentrations, it increases the ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC) during the actively growing period (25 days after anthesis). Indeed, exogenous application of the CK analogue kinetin to salinized actively growing fruits recovered sucrolytic activities (mainly cwInv and sucrose synthase), sink strength, and fruit weight, whereas the ethylene-releasing compound ethephon had a negative effect in equivalent non-stressed fruits. Fruit yield was increased by both the constitutive expression of CIN1 in the fruits (up to 4-fold) or IPT in the root (up to 30%), owing to an increase in the fruit number (lower flower abortion) and in fruit weight. This is possibly related to a recovery of sink activity in reproductive tissues due to both (i) increase in sucrolytic activities (cwInv, sucrose synthase, and vacuolar and cytoplasmic invertases) and tZ concentration, and (ii) a decrease in the ACC levels and the activity of the invertase inhibitor. This study provides new functional evidences about the role of

  18. Herbicide clomazone effects on δ-aminolevulinic acid activity and metabolic parameters in Cyprinus carpio.

    PubMed

    Menezes, Charlene; Leitemperger, Jossiele; Murussi, Camila; Toni, Cândida; Araújo, Maria do Carmo Santos; Farias, Iria Luiza; Perazzo, Giselle Xavier; Barbosa, Nilda Vargas; Loro, Vania Lucia

    2014-04-01

    The objective of this study was to investigate δ-aminolevulinic acid (δ-ALA-D) activity and metabolic parameters of Cyprinus carpio exposed to clomazone herbicide. Fish were exposed 2.5, 5, 10 and 20 mg L(-1) of clomazone for 192 h. Results indicated that δ-ALA-D activity was decreased in the gills at concentrations of 5 and 10 mg L(-1). Liver glycogen increased, while muscle and gill glycogen levels decreased at 5, 10 and 20 mg L(-1). Glucose was increased in the gills and plasma. Lactate decreased in the gills and liver and increased in the muscle. Protein and amino acids levels increased in the liver and gills and decreased in the muscle. At a clomazone concentration of 20 mg L(-1), ammonia increased in the gills and muscle and decreased in the liver. The results indicated that the metabolic parameters of glycogen, lactate, protein and amino acids in liver, muscle and gills, blood glucose levels, and the enzyme δ-ALA-D in gills may be useful indicators of clomazone toxicity in carp.

  19. Ubc9 Impairs Activation of the Brown Fat Energy Metabolism Program in Human White Adipocytes.

    PubMed

    Hartig, Sean M; Bader, David A; Abadie, Kathleen V; Motamed, Massoud; Hamilton, Mark P; Long, Weiwen; York, Brian; Mueller, Michaela; Wagner, Martin; Trauner, Michael; Chan, Lawrence; Bajaj, Mandeep; Moore, David D; Mancini, Michael A; McGuire, Sean E

    2015-09-01

    Insulin resistance and type 2 diabetes mellitus (T2DM) result from an inability to efficiently store and catabolize surplus energy in adipose tissue. Subcutaneous adipocytes protect against insulin resistance and T2DM by coupling differentiation with the induction of brown fat gene programs for efficient energy metabolism. Mechanisms that disrupt these programs in adipocytes are currently poorly defined, but represent therapeutic targets for the treatment of T2DM. To gain insight into these mechanisms, we performed a high-throughput microscopy screen that identified ubiquitin carrier protein 9 (Ubc9) as a negative regulator of energy storage in human sc adipocytes. Ubc9 depletion enhanced energy storage and induced the brown fat gene program in human sc adipocytes. Induction of adipocyte differentiation resulted in decreased Ubc9 expression commensurate with increased brown fat gene expression. Thiazolidinedione treatment reduced the interaction between Ubc9 and peroxisome proliferator-activated receptor (PPAR)γ, suggesting a mechanism by which Ubc9 represses PPARγ activity. In support of this hypothesis, Ubc9 overexpression remodeled energy metabolism in human sc adipocytes by selectively inhibiting brown adipocyte-specific function. Further, Ubc9 overexpression decreased uncoupling protein 1 expression by disrupting PPARγ binding at a critical uncoupling protein 1 enhancer region. Last, Ubc9 is significantly elevated in sc adipose tissue isolated from mouse models of insulin resistance as well as diabetic and insulin-resistant humans. Taken together, our findings demonstrate a critical role for Ubc9 in the regulation of sc adipocyte energy homeostasis.

  20. A computational model of adipose tissue metabolism: Evidence for intracellular compartmentation and differential activation of lipases

    PubMed Central

    Kim, Jaeyeon; Saidel, Gerald M.; Kalhan, Satish C.

    2008-01-01

    Regulation of lipolysis in adipose tissue is critical to whole body fuel homeostasis and to the development of insulin resistance. Due to the challenging nature of laboratory investigations of regulatory mechanisms in adipose tissue, mathematical models could provide a valuable adjunct to such experimental work. We have developed a computational model to analyze key components of adipose tissue metabolism in vivo in human in the fasting state. The various key components included triglyceride-fatty acid cycling, regulation of lipolytic reactions, and glyceroneogenesis. The model, consisting of spatially lumped blood and cellular compartments, included essential transport processes and biochemical reactions. Concentration dynamics for major substrates were described by mass balance equations. Model equations were solved numerically to simulate dynamic responses to intravenous epinephrine infusion. Model simulations were compared with the corresponding experimental measurements of the arteriovenous difference across the abdominal subcutaneous fat bed in humans. The model can simulate physiological responses arising from the different expression levels of lipases. Key findings of this study are as follows: (1) Distinguishing the active metabolic subdomain (~3% of total tissue volume) is critical for simulating data. (2) During epinephrine infusion, lipases are differentially activated such that diglyceride breakdown is ~4 times faster than triglyceride breakdown. (3) Glyceroneogenesis contributes more to glycerol-3-phosphate synthesis during epinephrine infusion when pyruvate oxidation is inhibited by a high acetyl-CoA/free-CoA ratio. PMID:18234232

  1. Chronic Ethanol Consumption Inhibits Glucokinase Transcriptional Activity by Atf3 and Triggers Metabolic Syndrome in Vivo*

    PubMed Central

    Kim, Ji Yeon; Hwang, Joo-Yeon; Lee, Dae Yeon; Song, Eun Hyun; Park, Keon Jae; Kim, Gyu Hee; Jeong, Eun Ae; Lee, Yoo Jeong; Go, Min Jin; Kim, Dae Jin; Lee, Seong Su; Kim, Bong-Jo; Song, Jihyun; Roh, Gu Seob; Gao, Bin; Kim, Won-Ho

    2014-01-01

    Chronic ethanol consumption induces pancreatic β-cell dysfunction through glucokinase (Gck) nitration and down-regulation, leading to impaired glucose tolerance and insulin resistance, but the underlying mechanism remains largely unknown. Here, we demonstrate that Gck gene expression and promoter activity in pancreatic β-cells were suppressed by chronic ethanol exposure in vivo and in vitro, whereas expression of activating transcription factor 3 (Atf3) and its binding to the putative Atf/Creb site (from −287 to −158 bp) on the Gck promoter were up-regulated. Furthermore, in vitro ethanol-induced Atf3 inhibited the positive effect of Pdx-1 on Gck transcriptional regulation, enhanced recruitment of Hdac1/2 and histone H3 deacetylation, and subsequently augmented the interaction of Hdac1/Pdx-1 on the Gck promoter, which were diminished by Atf3 siRNA. In vivo Atf3-silencing reversed ethanol-mediated Gck down-regulation and β-cell dysfunction, followed by the amelioration of impaired glucose tolerance and insulin resistance. Together, we identified that ethanol-induced Atf3 fosters β-cell dysfunction via Gck down-regulation and that its loss ameliorates metabolic syndrome and could be a potential therapeutic target in treating type 2 diabetes. The Atf3 gene is associated with the induction of type 2 diabetes and alcohol consumption-induced metabolic impairment and thus may be the major negative regulator for glucose homeostasis. PMID:25074928

  2. Spatial Distribution of the Metabolically Active Microbiota within Italian PDO Ewes' Milk Cheeses

    PubMed Central

    De Pasquale, Ilaria; Di Cagno, Raffaella; Buchin, Solange; De Angelis, Maria; Gobbetti, Marco

    2016-01-01

    Italian PDO (Protected Designation of Origin) Fiore Sardo (FS), Pecorino Siciliano (PS) and Pecorino Toscano (PT) ewes’ milk cheeses were chosen as hard cheese model systems to investigate the spatial distribution of the metabolically active microbiota and the related effects on proteolysis and synthesis of volatile components (VOC). Cheese slices were divided in nine sub-blocks, each one separately subjected to analysis and compared to whole cheese slice (control). Gradients for moisture, and concentrations of salt, fat and protein distinguished sub-blocks, while the cell density of the main microbial groups did not differ. Secondary proteolysis differed between sub-blocks of each cheese, especially when the number and area of hydrophilic and hydrophobic peptide peaks were assessed. The concentration of free amino acids (FAA) agreed with these data. As determined through Purge and Trap (PT) coupled with Gas Chromatography-Mass Spectrometry (PT-GC/MS), and regardless of the cheese variety, the profile with the lowest level of VOC was restricted to the region identified by the letter E defined as core. As shown through pyrosequencing of the 16S rRNA targeting RNA, the spatial distribution of the metabolically active microbiota agreed with the VOC distribution. Differences were highlighted between core and the rest of the cheese. Top and bottom under rind sub-blocks of all three cheeses harbored the widest biodiversity. The cheese sub-block analysis revealed the presence of a microbiota statistically correlated with secondary proteolysis events and/or synthesis of VOC. PMID:27073835

  3. Alimentary Habits, Physical Activity, and Framingham Global Risk Score in Metabolic Syndrome

    PubMed Central

    Soares, Thays Soliman; Piovesan, Carla Haas; Gustavo, Andréia da Silva; Macagnan, Fabrício Edler; Bodanese, Luiz Carlos; Feoli, Ana Maria Pandolfo

    2014-01-01

    Background Metabolic syndrome is a complex disorder represented by a set of cardiovascular risk factors. A healthy lifestyle is strongly related to improve Quality of Life and interfere positively in the control of risk factors presented in this condition. Objective To evaluate the effect of a program of lifestyle modification on the Framingham General Cardiovascular Risk Profile in subjects diagnosed with metabolic syndrome. Methods A sub-analysis study of a randomized clinical trial controlled blind that lasted three months. Participants were randomized into four groups: dietary intervention + placebo (DIP), dietary intervention + supplementation of omega 3 (fish oil 3 g/day) (DIS3), dietary intervention + placebo + physical activity (DIPE) and dietary intervention + physical activity + supplementation of omega 3 (DIS3PE). The general cardiovascular risk profile of each individual was calculated before and after the intervention. Results The study included 70 subjects. Evaluating the score between the pre and post intervention yielded a significant value (p < 0.001). We obtained a reduction for intermediate risk in 25.7% of subjects. After intervention, there was a significant reduction (p < 0.01) on cardiovascular age, this being more significant in groups DIP (5.2%) and DIPE (5.3%). Conclusion Proposed interventions produced beneficial effects for reducing cardiovascular risk score. This study emphasizes the importance of lifestyle modification in the prevention and treatment of cardiovascular diseases. PMID:24652053

  4. Ubc9 Impairs Activation of the Brown Fat Energy Metabolism Program in Human White Adipocytes

    PubMed Central

    Bader, David A.; Abadie, Kathleen V.; Motamed, Massoud; Hamilton, Mark P.; Long, Weiwen; York, Brian; Mueller, Michaela; Wagner, Martin; Trauner, Michael; Chan, Lawrence; Bajaj, Mandeep; Moore, David D.; Mancini, Michael A.; McGuire, Sean E.

    2015-01-01

    Insulin resistance and type 2 diabetes mellitus (T2DM) result from an inability to efficiently store and catabolize surplus energy in adipose tissue. Subcutaneous adipocytes protect against insulin resistance and T2DM by coupling differentiation with the induction of brown fat gene programs for efficient energy metabolism. Mechanisms that disrupt these programs in adipocytes are currently poorly defined, but represent therapeutic targets for the treatment of T2DM. To gain insight into these mechanisms, we performed a high-throughput microscopy screen that identified ubiquitin carrier protein 9 (Ubc9) as a negative regulator of energy storage in human sc adipocytes. Ubc9 depletion enhanced energy storage and induced the brown fat gene program in human sc adipocytes. Induction of adipocyte differentiation resulted in decreased Ubc9 expression commensurate with increased brown fat gene expression. Thiazolidinedione treatment reduced the interaction between Ubc9 and peroxisome proliferator-activated receptor (PPAR)γ, suggesting a mechanism by which Ubc9 represses PPARγ activity. In support of this hypothesis, Ubc9 overexpression remodeled energy metabolism in human sc adipocytes by selectively inhibiting brown adipocyte-specific function. Further, Ubc9 overexpression decreased uncoupling protein 1 expression by disrupting PPARγ binding at a critical uncoupling protein 1 enhancer region. Last, Ubc9 is significantly elevated in sc adipose tissue isolated from mouse models of insulin resistance as well as diabetic and insulin-resistant humans. Taken together, our findings demonstrate a critical role for Ubc9 in the regulation of sc adipocyte energy homeostasis. PMID:26192107

  5. Spatial Distribution of the Metabolically Active Microbiota within Italian PDO Ewes' Milk Cheeses.

    PubMed

    De Pasquale, Ilaria; Di Cagno, Raffaella; Buchin, Solange; De Angelis, Maria; Gobbetti, Marco

    2016-01-01

    Italian PDO (Protected Designation of Origin) Fiore Sardo (FS), Pecorino Siciliano (PS) and Pecorino Toscano (PT) ewes' milk cheeses were chosen as hard cheese model systems to investigate the spatial distribution of the metabolically active microbiota and the related effects on proteolysis and synthesis of volatile components (VOC). Cheese slices were divided in nine sub-blocks, each one separately subjected to analysis and compared to whole cheese slice (control). Gradients for moisture, and concentrations of salt, fat and protein distinguished sub-blocks, while the cell density of the main microbial groups did not differ. Secondary proteolysis differed between sub-blocks of each cheese, especially when the number and area of hydrophilic and hydrophobic peptide peaks were assessed. The concentration of free amino acids (FAA) agreed with these data. As determined through Purge and Trap (PT) coupled with Gas Chromatography-Mass Spectrometry (PT-GC/MS), and regardless of the cheese variety, the profile with the lowest level of VOC was restricted to the region identified by the letter E defined as core. As shown through pyrosequencing of the 16S rRNA targeting RNA, the spatial distribution of the metabolically active microbiota agreed with the VOC distribution. Differences were highlighted between core and the rest of the cheese. Top and bottom under rind sub-blocks of all three cheeses harbored the widest biodiversity. The cheese sub-block analysis revealed the presence of a microbiota statistically correlated with secondary proteolysis events and/or synthesis of VOC. PMID:27073835

  6. Hypoxic repression of pyruvate dehydrogenase activity is necessary for metabolic reprogramming and growth of model tumours.

    PubMed

    Golias, Tereza; Papandreou, Ioanna; Sun, Ramon; Kumar, Bhavna; Brown, Nicole V; Swanson, Benjamin J; Pai, Reetesh; Jaitin, Diego; Le, Quynh-Thu; Teknos, Theodoros N; Denko, Nicholas C

    2016-01-01

    Tumour cells fulfil the bioenergetic and biosynthetic needs of proliferation using the available environmental metabolites. Metabolic adaptation to hypoxia causes decreased mitochondrial function and increased lactate production. This work examines the biological importance of the hypoxia-inducible inhibitory phosphorylations on the pyruvate dehydrogenase E1α subunit. Pancreatic cancer cell lines were genetically manipulated to alter the net phosphorylation of PDH E1α through reduced kinase expression or enhanced phosphatase expression. The modified cells were tested for hypoxic changes in phosphorylated E1α, mitochondrial metabolism and growth as xenografted tumours. Even though there are four PDHK genes, PDHK1 is essential for inhibitory PDH phosphorylation of E1α at serine 232, is partially responsible for modification of serines 293 and 300, and these phosphorylations are necessary for model tumour growth. In order to determine the clinical relevance, a cohort of head and neck cancer patient biopsies was examined for phosphorylated E1α and expression of PDHK1. Patients with detectable 232 phosphorylation or expression of PDHK1 tend to have worse clinical outcome. These data show that PDHK1 activity is unique and non-redundant in the family of PHDK enzymes and a PDHK1 specific inhibitor would therefore have anti-cancer activity with reduced chance of side effects from inhibition of other PDHKs. PMID:27498883

  7. Hypoxic repression of pyruvate dehydrogenase activity is necessary for metabolic reprogramming and growth of model tumours

    PubMed Central

    Golias, Tereza; Papandreou, Ioanna; Sun, Ramon; Kumar, Bhavna; Brown, Nicole V.; Swanson, Benjamin J.; Pai, Reetesh; Jaitin, Diego; Le, Quynh-Thu; Teknos, Theodoros N.; Denko, Nicholas C.

    2016-01-01

    Tumour cells fulfil the bioenergetic and biosynthetic needs of proliferation using the available environmental metabolites. Metabolic adaptation to hypoxia causes decreased mitochondrial function and increased lactate production. This work examines the biological importance of the hypoxia-inducible inhibitory phosphorylations on the pyruvate dehydrogenase E1α subunit. Pancreatic cancer cell lines were genetically manipulated to alter the net phosphorylation of PDH E1α through reduced kinase expression or enhanced phosphatase expression. The modified cells were tested for hypoxic changes in phosphorylated E1α, mitochondrial metabolism and growth as xenografted tumours. Even though there are four PDHK genes, PDHK1 is essential for inhibitory PDH phosphorylation of E1α at serine 232, is partially responsible for modification of serines 293 and 300, and these phosphorylations are necessary for model tumour growth. In order to determine the clinical relevance, a cohort of head and neck cancer patient biopsies was examined for phosphorylated E1α and expression of PDHK1. Patients with detectable 232 phosphorylation or expression of PDHK1 tend to have worse clinical outcome. These data show that PDHK1 activity is unique and non-redundant in the family of PHDK enzymes and a PDHK1 specific inhibitor would therefore have anti-cancer activity with reduced chance of side effects from inhibition of other PDHKs. PMID:27498883

  8. Litter Environment Affects Behavior and Brain Metabolic Activity of Adult Knockout Mice

    PubMed Central

    Crews, David; Rushworth, David; Gonzalez-Lima, Francisco; Ogawa, Sonoko

    2009-01-01

    In mammals, the formative environment for social and anxiety-related behaviors is the family unit; in the case of rodents, this is the litter and the mother-young bond. A deciding factor in this environment is the sex ratio of the litter and, in the case of mice lacking functional copies of gene(s), the ratio of the various genotypes in the litter. Both Sex and Genotype ratios of the litter affect the nature and quality of the individual's behavior later in adulthood, as well as metabolic activity in brain nuclei that underlie these behaviors. Mice were raised in litters reconstituted shortly after to birth to control for sex ratio and genotype ratio (wild type pups versus pups lacking a functional estrogen receptor α). In both males and females, the Sex and Genotype of siblings in the litter affected aggressive behaviors as well as patterns of metabolic activity in limbic nuclei in the social behavior network later in adulthood. Further, this pattern in males varied depending upon the Genotype of their brothers and sisters. Principal Components Analysis revealed two components comprised of several amygdalar and hypothalamic nuclei; the VMH showed strong correlations in both clusters, suggesting its pivotal nature in the organization of two neural networks. PMID:19707539

  9. The bacterial cytoplasm has glass-like properties and is fluidized by metabolic activity

    NASA Astrophysics Data System (ADS)

    Parry, Brad; Surovtsev, Ivan; Cabeen, Matthew; O'Hern, Corey; Dufresne, Eric; Jacobs-Wagner, Christine

    2014-03-01

    In eukaryotes, active transport involves motor proteins and cytoskeletal filaments. In contrast, bacteria (which lack cytoskeletal motor proteins) are thought to rely on diffusion for molecular transport, though the physical properties of the bacterial cytoplasm are poorly understood. Through single particle tracking of foreign particles of different sizes, we have found that the bacterial cytoplasm exhibits striking similarities to glass-forming liquids. Glass-forming liquids are noted for their metastability near the glass transition where their behavior changes from liquid-like to amorphous solid with even small perturbations. Particles of different sizes exhibit distinct dynamics and their mobility changes from fluid-like to glassy with increasing size. This size dependency provides an explanation for previous reports of both normal and anomalous diffusion in the bacterial cytoplasm. Moreover, we find that cellular metabolism attenuates the glassy properties of the bacterial cytoplasm. As a result, components that would otherwise be caged in narrow regions of confinement are able to explore the cytoplasmic space under metabolically active conditions. These findings have broad implications for our understanding of bacterial physiology as the glassy behavior of the cytoplasm impacts all intracellular processes involving large cellular components. Supported by the Howard Hughes Medical Institute.

  10. Comparative analysis of fecal microbiota and intestinal microbial metabolic activity in captive polar bears.

    PubMed

    Schwab, Clarissa; Gänzle, Michael

    2011-03-01

    The composition of the intestinal microbiota depends on gut physiology and diet. Ursidae possess a simple gastrointestinal system composed of a stomach, small intestine, and indistinct hindgut. This study determined the composition and stability of fecal microbiota of 3 captive polar bears by group-specific quantitative PCR and PCR-DGGE (denaturing gradient gel electrophoresis) using the 16S rRNA gene as target. Intestinal metabolic activity was determined by analysis of short-chain fatty acids in feces. For comparison, other Carnivora and mammals were included in this study. Total bacterial abundance was approximately log 8.5 DNA gene copies·(g feces)-1 in all 3 polar bears. Fecal polar bear microbiota was dominated by the facultative anaerobes Enterobacteriaceae and enterococci, and the Clostridium cluster I. The detection of the Clostridium perfringens α-toxin gene verified the presence of C. perfringens. Composition of the fecal bacterial population was stable on a genus level; according to results obtained by PCR-DGGE, dominant bacterial species fluctuated. The total short-chain fatty acid content of Carnivora and other mammals analysed was comparable; lactate was detected in feces of all carnivora but present only in trace amounts in other mammals. In comparison, the fecal microbiota and metabolic activity of captive polar bears mostly resembled the closely related grizzly and black bears.

  11. Comparative analysis of fecal microbiota and intestinal microbial metabolic activity in captive polar bears.

    PubMed

    Schwab, Clarissa; Gänzle, Michael

    2011-03-01

    The composition of the intestinal microbiota depends on gut physiology and diet. Ursidae possess a simple gastrointestinal system composed of a stomach, small intestine, and indistinct hindgut. This study determined the composition and stability of fecal microbiota of 3 captive polar bears by group-specific quantitative PCR and PCR-DGGE (denaturing gradient gel electrophoresis) using the 16S rRNA gene as target. Intestinal metabolic activity was determined by analysis of short-chain fatty acids in feces. For comparison, other Carnivora and mammals were included in this study. Total bacterial abundance was approximately log 8.5 DNA gene copies·(g feces)-1 in all 3 polar bears. Fecal polar bear microbiota was dominated by the facultative anaerobes Enterobacteriaceae and enterococci, and the Clostridium cluster I. The detection of the Clostridium perfringens α-toxin gene verified the presence of C. perfringens. Composition of the fecal bacterial population was stable on a genus level; according to results obtained by PCR-DGGE, dominant bacterial species fluctuated. The total short-chain fatty acid content of Carnivora and other mammals analysed was comparable; lactate was detected in feces of all carnivora but present only in trace amounts in other mammals. In comparison, the fecal microbiota and metabolic activity of captive polar bears mostly resembled the closely related grizzly and black bears. PMID:21358758

  12. Parenchyma cell respiration and survival in secondary xylem: does metabolic activity decline with cell age?

    PubMed

    Spicer, R; Holbrook, N M

    2007-08-01

    Sapwood respiration often declines towards the sapwood/heartwood boundary, but it is not known if parenchyma metabolic activity declines with cell age. We measured sapwood respiration in five temperate species (sapwood age range of 5-64 years) and expressed respiration on a live cell basis by quantifying living parenchyma. We found no effect of parenchyma age on respiration in two conifers (Pinus strobus, Tsuga canadensis), both of which had significant amounts of dead parenchyma in the sapwood. In angiosperms (Acer rubrum, Fraxinus americana, Quercus rubra), both bulk tissue and live cell respiration were reduced by about one-half in the oldest relative to the youngest sapwood, and all sapwood parenchyma remained alive. Conifers and angiosperms had similar bulk tissue respiration despite a smaller proportion of parenchyma in conifers (5% versus 15-25% in angiosperms), such that conifer parenchyma respired at rates about three times those of angiosperms. The fact that 5-year-old parenchyma cells respired at the same rate as 25-year-old cells in conifers suggests that there is no inherent or intrinsic decline in respiration as a result of cellular ageing. In contrast, it is not known whether differences observed in cellular respiration rates of angiosperms are a function of age per se, or whether active regulation of metabolic rate or positional effects (e.g. proximity to resources and/or hormones) could be the cause of reduced respiration in older sapwood.

  13. (±)-Japonicols A-D, Acylphloroglucinol-Based Meroterpenoid Enantiomers with Anti-KSHV Activities from Hypericum japonicum.

    PubMed

    Hu, Linzhen; Xue, Yongbo; Zhang, Jinwen; Zhu, Hucheng; Chen, Chunmei; Li, Xiao-Nian; Liu, Junjun; Wang, Zhenzhen; Zhang, Yu; Zhang, Yonghui

    2016-05-27

    (±)-Japonicols A-D (1a/1b-4a/4b), four pairs of new phloroglucinol-based terpenoid enantiomers, were isolated from Hypericum japonicum. Their absolute configurations were confirmed through comparison of their experimental and calculated electronic circular dichroism spectra and single-crystal X-ray diffraction analyses. Compounds 1a/1b, 2a/2b, and 3a/3b possess 2-oxabicyclo[3.3.1]nonane, pyrano[3,2-b]pyran, and benzo[b]cyclopenta[e]oxepine ring systems, respectively. The effects of the phloroglucinols on anti-Kaposi's sarcoma-associated herpesvirus were assessed, and 2a exhibited a moderate inhibitory effect, with an EC50 value of 8.75 μM and a selectivity index of 16.06. PMID:27116034

  14. Glucocorticoid activity and metabolism with NaCl-induced low-grade metabolic acidosis and oral alkalization: results of two randomized controlled trials.

    PubMed

    Buehlmeier, Judith; Remer, Thomas; Frings-Meuthen, Petra; Maser-Gluth, Christiane; Heer, Martina

    2016-04-01

    Low-grade metabolic acidosis (LGMA), as induced by high dietary acid load or sodium chloride (NaCl) intake, has been shown to increase bone and protein catabolism. Underlying mechanisms are not fully understood, but from clinical metabolic acidosis interactions of acid-base balance with glucocorticoid (GC) metabolism are known. We aimed to investigate GC activity/metabolism under alkaline supplementation and NaCl-induced LGMA. Eight young, healthy, normal-weight men participated in two crossover designed interventional studies. In Study A, two 10-day high NaCl diet (32 g/d) periods were conducted, one supplemented with 90 mmol KHCO3/day. In Study B, participants received a high and a low NaCl diet (31 vs. 3 g/day), each for 14 days. During low NaCl, the diet was moderately acidified by replacement of a bicarbonate-rich mineral water (consumed during high NaCl) with a non-alkalizing drinking water. In repeatedly collected 24-h urine samples, potentially bioactive-free GCs (urinary-free cortisol + free cortisone) were analyzed, as well as tetrahydrocortisol (THF), 5α-THF, and tetrahydrocortisone (THE). With supplementation of 90 mmol KHCO3, the marker of total adrenal GC secretion (THF + 5α-THF + THE) dropped (p = 0.047) and potentially bioactive-free GCs were reduced (p = 0.003). In Study B, however, GC secretion and potentially bioactive-free GCs did not exhibit the expected fall with NaCl-reduction as net acid excretion was raised by 30 mEq/d. Diet-induced acidification/alkalization affects GC activity and metabolism, which in case of long-term ingestion of habitually acidifying western diets may constitute an independent risk factor for bone degradation and cardiometabolic diseases. PMID:26349936

  15. Relation between presence-absence of a visible nucleoid and metabolic activity in bacterioplankton cells

    SciTech Connect

    Choi, Joon, W.; Sherr, E.B.; Sherr, B.F.

    1996-09-01

    We investigated the report of Zweifel and Hagstroem that only a portion of marine bacteria contain nucleoids--the DNA-containing regions of procaryotic cells-- and that such bacteria correspond to the active or viable fraction of bacterioplankton. In Oregon coastal waters, 21-64% of bacteria had visible nucleoids; number of nucleoid-visible (NV) bacteria were greater than numbers of metabolically active bacteria, based on cells with active electron transport systems (ETS) and intact cell membranes. During log growth of a marine isolate, proportions of NV and ETS-active cells approached 100%. In stationary growth phase, the fraction of ETS-active cells decreased rapidly, while that of NV cells remained high for 7 d. When starved cells of the isolate were resupplied with nutrient (50 mg liter{sup -1} peptone), total cell number did not increase during the initial 6 h, but the proportion of NV cells increased from 27 to 100%, and that of ETS-active cells from 6 to 75%. In an analogous experiment with a bacterioplankton assemblage, a similar trend was observed: the number of NV cells double during the initial 6 h prior to an increase in total cell counts. These results show that some bacteria without visible nucleoids are capable of becoming NV cells, and thus have DNa in a nucleoid region not detectable with the method used here. 18 refs., 4 figs., 1 tab.

  16. Altered kynurenine pathway metabolism in autism: Implication for immune-induced glutamatergic activity.

    PubMed

    Lim, Chai K; Essa, Musthafa M; de Paula Martins, Roberta; Lovejoy, David B; Bilgin, Ayse A; Waly, Mostafa I; Al-Farsi, Yahya M; Al-Sharbati, Marwan; Al-Shaffae, Mohammed A; Guillemin, Gilles J

    2016-06-01

    Dysfunction of the serotoninergic and glutamatergic systems is implicated in the pathogenesis of autism spectrum disorder (ASD) together with various neuroinflammatory mediators. As the kynurenine pathway (KP) of tryptophan degradation is activated in neuroinflammatory states, we hypothesized that there may